ASPD is considered to be among the most difficult personality disorders to treat. Because of their very low or absent capacity for remorse, individuals with ASPD often lack sufficient motivation and fail to see the costs associated with antisocial acts. They may only simulate remorse rather than truly commit to change: they can be seductively charming and dishonest, and may manipulate staff and fellow patients during treatment. Studies have shown that outpatient therapy is not likely to be successful, but the extent to which persons with ASPD are entirely unresponsive to treatment may have been exaggerated.

Those with ASPD may stay in treatment only as required by an external source, such as parole conditions. Residential programs that provide a carefully controlled environment of structure and supervision along with peer confrontation have been recommended. There has been some research on the treatment of ASPD that indicated positive results for therapeutic interventions.

Psychotherapy also known as talk therapy is found to help treat patients with ASPD.Schema therapy is also being investigated as a treatment for ASPD. A review by Charles M. Borduin features the strong influence of Multisystemic therapy (MST) that could potentially improve this imperative issue. However, this treatment requires complete cooperation and participation of all family members. Some studies have found that the presence of ASPD does not significantly interfere with treatment for other disorders, such as substance abuse, although others have reported contradictory findings.

Therapists working with individuals with ASPD may have considerable negative feelings toward patients with extensive histories of aggressive, exploitative, and abusive behaviors. Rather than attempt to develop a sense of conscience in these individuals, which is extremely difficult considering the nature of the disorder, therapeutic techniques are focused on rational and utilitarian arguments against repeating past mistakes. These approaches would focus on the tangible, material value of prosocial behavior and abstaining from antisocial behavior. However, the impulsive and aggressive nature of those with this disorder may limit the effectiveness of even this form of therapy.

The use of medications in treating antisocial personality disorder is still poorly explored, and no medications have been approved by the FDA to specifically treat ASPD. A 2010 Cochrane review of studies that explored the use of pharmaceuticals in ASPD patients, of which 8 studies met the selection criteria for review, concluded that the current body of evidence was inconclusive for recommendations concerning the use of pharmaceuticals in treating the various issues of ASPD. Nonetheless psychiatric medications such as antipsychotics, antidepressants, and mood stabilizers can be used to control symptoms such as aggression and impulsivity, as well as treat disorders that may co-occur with ASPD for which medications are indicated.

According to Professor Emily Simonoff of the Institute of Psychiatry, Psychology and Neuroscience, "childhood hyperactivity and conduct disorder showed equally strong prediction of antisocial personality disorder (ASPD) and criminality in early and mid-adult life. Lower IQ and reading problems were most prominent in their relationships with childhood and adolescent antisocial behaviour."