There are 4 aspects to the treatment of angular cheilitis. Firstly, potential reservoirs of infection inside the mouth are identified and treated. Oral candidiasis, especially denture-related stomatitis is often found to be present where there is angular cheilitis, and if it is not treated, the sores at the corners of the mouth may often recur. This involves having dentures properly fitted and disinfected. Commercial preparations are marketed for this purpose, although dentures may be left in dilute (1:10 concentration) household bleach overnight, but only if they are entirely plastic and do not contain any metal parts, and with rinsing under clean water before use. Improved denture hygiene is often required thereafter, including not wearing the denture during sleep and cleaning it daily. For more information, see Denture-related stomatitis.

Secondly, there may be a need to increase the vertical dimension of the lower face to prevent overclosure of the mouth and formation of deep skin folds. This may require the construction of a new denture with an adjusted bite. Rarely, in cases resistant to normal treatments, surgical procedures such as collagen injections (or other facial fillers such as autologous fat or crosslinked hyaluronic acid) are used in an attempt to restore the normal facial contour. Other measures which seek to reverse the local factors that may be contributing to the condition include improving oral hygiene, stopping smoking or other tobacco habits and use of a barrier cream (e.g. zinc oxide paste) at night.

Thirdly, treatment of the infection and inflammation of the lesions themselves is addressed. This is usually with topical antifungal medication, such as clotrimazole, amphotericin B, ketoconazole, or nystatin cream. Some antifungal creams are combined with corticosteroids such as hydrocortisone or triamcinolone to reduce inflammation, and certain antifungals such as miconazole also have some antibacterial action. Diiodohydroxyquinoline is another topical therapy for angular cheilitis. If "Staphylococcus aureus" infection is demonstrated by microbiological culture to be responsible (or suspected), the treatment may be changed to fusidic acid cream, an antibiotic which is effective against this type of bacteria. Aside from fusidic acid, neomycin, mupirocin, metronidazole, and chlorhexidine are alternative options in this scenario.

Finally, if the condition appears resistant to treatment, investigations for underlying causes such as anemia or nutrient deficiencies or HIV infection. Identification of the underlying cause is essential for treating chronic cases. The lesions may resolve when the underlying disease is treated, e.g. with a course of oral iron or B vitamin supplements. Patch testing is recommended by some in cases which are resistant to treatment and where allergic contact dermatitis is suspected.

The most important aspect of treatment is improving denture hygiene, i.e. removing the denture at night, cleaning and disinfecting it, and storing it overnight in an antiseptic solution. This is important as the denture is usually infected with "C. albicans" which will cause re-infection if it is not removed. Substances which are used include solutions of alkaline peroxides, alkaline hypochlorites (e.g. hypochlorite, which may over time corrode metal components of dental appliances), acids (e.g. benzoic acid), yeast lytic enzymes and proteolytic enzymes (e.g. alcalase protease). The other aspect of treatment involves resolution of the mucosal infection, for which topical antifungal medications are used (e.g. nystatin, amphotericin, miconazole, fluconazole or itraconazole). Often an antimicrobial mouthwash such as chlorhexidine is concurrently prescribed. Possible underlying disease (diabetes, HIV) should be treated where possible.

The goal of treatment is to reduce inflammation. Treatment usually does not require hospitalization unless tongue swelling is severe. Good oral hygiene is necessary, including thorough tooth brushing at least twice a day, and flossing at least daily. Corticosteroids such as prednisone may be given to reduce the inflammation of glossitis. For mild cases, topical applications (such as a prednisone mouth rinse that is not swallowed) may be recommended to avoid the side effects of swallowed or injected corticosteroids. Antibiotics, antifungal medications, or other antimicrobials may be prescribed if the cause of glossitis is an infection. Anemia and nutritional deficiencies (such as a deficiency in niacin, riboflavin, iron, or Vitamin E) must be treated, often by dietary changes or other supplements. Avoid irritants (such as hot or spicy foods, alcohol, and tobacco) to minimize the discomfort.

In some cases, tongue swelling may threaten the airway, a medical emergency that needs immediate attention.

The first line therapy for aphthous stomatitis is topical agents rather than systemic medication, with topical corticosteroids being the mainstay treatment. Systemic treatment is usually reserved for severe disease due to the risk of adverse side effects associated with many of these agents. A systematic review found that no single systemic intervention was found to be effective. Good oral hygiene is important to prevent secondary infection of the ulcers.

Occasionally, in females where ulceration is correlated to the menstrual cycle or to birth control pills, progestogen or a change in birth control may be beneficial. Use of nicotine replacement therapy for people who have developed oral ulceration after stopping smoking has also been reported. Starting smoking again does not usually lessen the condition. Trauma can be reduced by avoiding rough or sharp foodstuffs and by brushing teeth with care. If sodium lauryl sulfate is suspected to be the cause, avoidance of products containing this chemical may be useful and prevent recurrence in some individuals. Similarly patch testing may indicate that food allergy is responsible, and the diet modified accordingly. If investigations reveal deficiency states, correction of the deficiency may result in resolution of the ulceration. For example, there is some evidence that vitamin B12 supplementation may prevent recurrence in some individuals.

The vast majority of people with aphthous stomatitis have minor symptoms and do not require any specific therapy. The pain is often tolerable with simple dietary modification during an episode of ulceration such as avoiding spicy and acidic foods and beverages. Many different topical and systemic medications have been proposed (see table), sometimes showing little or no evidence of usefulness when formally investigated. Some of the results of interventions for RAS may in truth represent a placebo effect. No therapy is curative, with treatment aiming to relieve pain, promote healing and reduce the frequency of episodes of ulceration.

Treatment is cause-related, but also symptomatic if the underlying cause is unknown or not correctable. It is also important to note that most ulcers will heal completely without any intervention. Treatment can range from simply smoothing or removing a local cause of trauma, to addressing underlying factors such as dry mouth or substituting a problem medication. Maintaining good oral hygiene and use of an antiseptic mouthwash or spray (e.g. chlorhexidine) can prevent secondary infection and therefore hasten healing. A topical analgesic (e.g. benzydamine mouthwash) may reduce pain. Topical (gels, creams or inhalers) or systemic steroids may be used to reduce inflammation. An antifungal drug may be used to prevent oral candidiasis developing in those who use prolonged steroids. People with mouth ulcers may prefer to avoid hot or spicy foods, which can increase the pain. Self-inflicted ulceration can be difficult to manage, and psychiatric input may be required in some people.

Most cases of angular cheilitis respond quickly when antifungal treatment is used. In more long standing cases, the severity of the condition often follows a relapsing and remitting course over time. The condition can be difficult to treat and can be prolonged.

Good oral hygiene (thorough tooth brushing and flossing and regular professional cleaning and examination) may be helpful to prevent these disorders. Drinking plenty of water and the production of enough saliva, aid in the reduction of bacterial growth. Minimizing irritants or injury in the mouth when possible can aid in the prevention of glossitis. Avoiding excessive use of any food or substance that irritates the mouth or tongue may also help.

Denture-related stomatitis is usually a harmless condition with no long term consequences. It usually resolves with simple measures such as improved denture hygiene or topical antifungal medication. In severely immunocompromised individuals (e.g. those with HIV), the infection may present a more serious threat.

Good denture hygiene involves regular cleaning of the dentures, and leaving them out of the mouth during sleep. This gives the mucosa a chance to recover, while wearing a denture during sleep is often likened to sleeping in one's shoes. In oral candidiasis, the dentures may act as a reservoir of Candida species, continually reinfecting the mucosa once antifungal medication is stopped. Therefore, they must be disinfected as part of the treatment for oral candidiasis. There are commercial denture cleaner preparations for this purpose, but it is readily accomplished by soaking the denture overnight in a 1:10 solution of sodium hypochlorite (Milton, or household bleach). Bleach may corrode metal components, so if the denture contains metal, soaking it twice daily in chlorhexidine solution can be carried out instead. An alternative method of disinfection is to use a 10% solution of acetic acid (vinegar) as an overnight soak, or to microwave the dentures in 200mL water for 3 minutes at 650 watts. Antifungal medication can also be applied to the fitting surface of the denture before it is put back in the mouth. Other problems with the dentures, such as inadequate occlusal vertical dimension may also need to be corrected in the case of angular cheilitis.

Oral candidiasis can be treated with topical anti-fungal drugs, such as nystatin, miconazole, Gentian violet or amphotericin B.

Underlying immunosuppression may be medically manageable once it is identified, and this helps prevent recurrence of candidal infections.

Patients who are immunocompromised, either with HIV/AIDS or as a result of chemotherapy, may require systemic treatment with oral or intravenous administered anti-fungals.

If candidiasis is secondary to corticosteroid or antibiotic use, then use may be stopped, although this is not always a feasible option. Candidiasis secondary to the use of inhaled steroids may be treated by rinsing out the mouth with water after taking the steroid. Use of a spacer device to reduce the contact with the oral mucosa may greatly reduce the risk of oral candidiasis.

In recurrent oral candidiasis, the use of azole antifungals risks selection and enrichment of drug-resistant strains of candida organisms. Drug resistance is increasingly more common and presents a serious problem in persons who are immunocompromised.

Prophylactic use of antifungals is sometimes employed in persons with HIV disease, during radiotherapy, during immunosuppressive or prolonged antibiotic therapy as the development of candidal infection in these groups may be more serious.

The candidal load in the mouth can be reduced by improving oral hygiene measures, such as regular toothbrushing and use of anti-microbial mouthwashes. Since smoking is associated with many of forms of oral candidiasis, cessation may be beneficial.

Topical 5-fluorouracil (5-FU, Efudex, Carac) has been shown to be an effective therapy for diffuse, but minor actinic cheilitis. 5-fluorouracil works by blocking DNA synthesis. Cells that are rapidly growing need more DNA, so they accumulate more 5-fluorouracil, resulting in their death. Normal skin is much less affected. The treatment usually takes 2–4 weeks depending on the response. The typical response includes an inflammatory phase, followed by redness, burning, oozing, and finally erosion. Treatment is stopped when ulceration and crusting appear. There is minimal scarring. Complete clearance has been reported in about 50% of patients.

Imiquimod (Aldara) is an immune response modifier that has been studied for the treatment of actinic cheilitis. It promotes an immune response in the skin leading to apoptosis (death) of the tumor cells. It causes the epidermis to be invaded by macrophages, which leads to epidermal erosion. T-cells are also activated as a result of imiquimod treatment. Imiquimod appears to promote an “immune memory” that reduces the recurrence of lesions. There is minimal scarring. Complete clearance has been demonstrated in up to 45% of patients with actinic keratoses. However, the dose and duration of therapy, as well as the long-term efficacy, still need to be established in the treatment of actinic cheilitis.

Anti-tumour necrosis factor α antagonists (e.g. infliximab)

Dietary restriction of a particular suspected or proven antigen may be involved in the management of OFG, such as cinnamon or benzoate-free diets.

This condition is considered premalignant because it may lead to squamous cell carcinoma in about 10% of all cases. It is not possible to predict which cases will progress into SCC, so the current consensus is that all lesions should be treated.

Treatment options include 5-fluorouracil, imiquimod, scalpel vermillionectomy, chemical peel, electrosurgery, and carbon dioxide laser vaporization. These curative treatments attempt to destroy or remove the damaged epithelium. All methods are associated with some degree of pain, edema, and a relatively low rate of recurrence.

Preventing exposure to the causative antigen leads to resolution of the condition. Tacrolimus or clobetasol propionate have also been used to treat plasma cell cheilitis.

Systemic candidiasis occurs when Candida yeast enters the bloodstream and may spread (becoming disseminated candidiasis) to other organs, including the central nervous system, kidneys, liver, bones, muscles, joints, spleen, or eyes. Treatment typically consists of oral or intravenous antifungal medications. In candidal infections of the blood, intravenous fluconazole or an echinocandin such as caspofungin may be used. Amphotericin B is another option.

Mouth and throat candidiasis are treated with antifungal medication. Oral candidiasis usually responds to topical treatments; otherwise, systemic antifungal medication may be needed for oral infections. Candidal skin infections in the skin folds (candidal intertrigo) typically respond well to topical antifungal treatments (e.g., nystatin or miconazole). Systemic treatment with antifungals by mouth is reserved for severe cases or if treatment with topical therapy is unsuccessful. Candida esophagitis may be treated orally or intravenously; for severe or azole-resistant esophageal candidiasis, treatment with amphotericin B may be necessary.

Vaginal yeast infections are typically treated with topical antifungal agents. A one-time dose of fluconazole is 90% effective in treating a vaginal yeast infection. For severe nonrecurring cases, several doses of fluconazole is recommended. Local treatment may include vaginal suppositories or medicated douches. Other types of yeast infections require different dosing. Gentian violet can be used for thrush in breastfeeding babies. "C. albicans" can develop resistance to fluconazole, this being more of an issue in those with HIV/AIDS who are often treated with multiple courses of fluconazole for recurrent oral infections.

For vaginal yeast infection in pregnancy, topical imidazole or triazole antifungals are considered the therapy of choice owing to available safety data. Systemic absorption of these topical formulations is minimal, posing little risk of transplacental transfer. In vaginal yeast infection in pregnancy, treatment with topical azole antifungals is recommended for 7 days instead of a shorter duration.

No benefit from probiotics has been found for active infections.

If a cause can be identified for a burning sensation in the mouth, then treatment of this underlying factor is recommended. If symptom persist despite treatment a diagnosis of BMS is confirmed. BMS has been traditionally treated by reassurance and with antidepressants, anxiolytics or anticonvulsants. A 2016 Cochrane review of treatment for burning mouth syndrome concluded that strong evidence of an effective treatment was not available. Other treatments which have been used include atypical antipsychotics, histamine receptor antagonists, and dopamine agonists.

Surgical removal of the lesion is the first choice of treatment for many clinicians. However, the efficacy of this treatment modality cannot be assessed due to insufficient available evidence. This can be carried out by traditional surgical excision with a scalpel, with lasers, or with eletrocautery or cryotherapy. Often if biopsy demonstrates moderate or severe dysplasia then the decision to excise them is taken more readily. Sometimes white patches are too large to remove completely and instead they are monitored closely. Even if the lesion is completely removed, long term review is still usually indicated since leukoplakia can recur, especially if predisposing factors such as smoking are not stopped.

Many different topical and systemic medications have been studied, including anti-inflammatories, antimycotics (target Candida species), carotenoids (precursors to vitamin A, e.g. beta carotene), retinoids (drugs similar to vitamin A), and cytotoxics, but none have evidence that they prevent malignant transformation in an area of leukoplakia.Vitamins C and E have also been studied with regards a therapy for leukoplakia. Some of this research is carried out based upon the hypothesis that antioxidant nutrients, vitamins and cell growth suppressor proteins (e.g. p53) are antagonistic to oncogenesis. High doses of retinoids may cause toxic effects. Other treatments that have been studied include photodynamic therapy.

Terms such as "plasma cell gingivostomatitis", "atypical gingivostomatitis" and "idiopathic gingivostomatitis" are sometimes a synonym for plasma cell gingivitis, or specifically to refer to a severe form of plasma cell gingivitis.

Common causes of drug-related cheilitis include Etretinate, Indinavir, Protease inhibitors, Vitamin A and Isotretinoin (a retinoid drug). Uncommon causes include Atorvastatin, Busulphan, Clofazimine, Clomipramine, Cyancobalamin, Gold, Methyldopa, Psoralens, Streptomycin, Sulfasalazine and Tetracycline. A condition called "drug-induced ulcer of the lip" is described as being characterized by painful or tender, well-defined ulcerations of the lip without induration. It is the result of oral administration of drugs, and the condition resolves when the drugs are stopped.

This is a rare inflammatory condition of the minor salivary glands, usually in the lower lip, which appears swollen and everted. There may also be ulceration, crusting, abscesses, and sinus tracts. It is an acquired disorder, but the cause is uncertain. Suspected causes include sunlight, tobacco, syphilis, poor oral hygiene and genetic factors. The openings of the minor salivary gland ducts become inflamed and dilated, and there may be mucopurulent discharge from the ducts. A previous classification suggested dividing cheilitis into 3 types based on severity, with the later stages involving secondary infection with bacteria, and increased ulceration, suppuration and swelling: Type 1, Simple; Type 2, Superficial suppurative ("Baelz's disease"); and Type 3, Deep suppurative ("cheilitis glandularis epostemetosa"). Cheilitis glandularis usually occurs in middle-aged and elderly males, and it carries a risk of malignant transformation to squamous cell carcinoma (18% to 35%). Preventative treatment such as vermilionectomy ("lip shave") is therefore the treatment of choice.

Stomatitis may also be caused by chemotherapy, or radiation therapy of the oropharyngeal area. The term "mucositis" is sometimes used synonymously with stomatitis, however the former usually refers to mucosal reactions to radiotherapy or chemotherapy, and may occur anywhere in the gastrointestinal tract and not just in the mouth.

Topical diclofenac sodium gel is a nonsteroidal anti-inflammatory drug that is thought to work in the treatment of AK through its inhibition of the arachidonic acid pathway, thereby limiting the production of prostaglandins which are thought to be involved in the development of UVB-induced skin cancers. Recommended duration of therapy is 60 to 90 days with twice daily application. Treatment of facial AK with diclofenac gel led to complete lesion resolution in 40% of cases. Common side effects include dryness, itching, redness, and rash at the site of application.