A goal of community base efforts is to eliminate microfilariae from the blood of infected individuals in order to prevent transmission to the mosquito. This is primarily accomplished through the use of drugs. The treatment for "B. malayi" infection is the same as for bancroftian filariasis. Diethylcarbamazine (DEC) has been used in mass treatment programs in the form of DEC-medicated salt, as an effective microfilaricidal drug in several locations, including India. While DEC tends to cause adverse reactions like immediate fever and weakness, it is not known to cause any long-term adverse drug effects. DEC has been shown to kill both adult worms and microfilariae. In Malaysia, DEC dosages (6 mg/kg weekly for 6 weeks; 6 mg/kg daily for 9 days) reduced microfilariae by 80% for 18–24 months after treatment in the absence of mosquito control. Microfilariae numbers slowly return many months after treatment, thus requiring multiple drug doses over time in order to achieve long-term control. However, it is not known how many years of mass drug administration is required to eliminate transmission. But currently, there have been no confirmed cases of DEC resistance.

Single doses of two drugs (albendazole-DEC and albendazole-ivermectin) have been shown to remove 99% of microfilariae for a year after treatment and help to improve elephantiasis during early stages of the disease. Ivermectin does not appear to kill adult worms but serves as a less toxic microfilaricide.

Since the discovery of the importance of "Wolbachia" bacteria in the life cycle of "B. malayi" and other nematodes, novel drug efforts have targeted the endobacterium. Tetracyclines, rifampicin, and chloramphenicol have been effective in vitro by interfering with larvae molting and microfilariae development. Tetracyclines have been shown to cause reproductive and embryogenesis abnormalities in the adult worms, resulting in worm sterility. Clinical trials have demonstrated the successful reduction of "Wolbachia" and microfilariae in onchocerciasis and "W. bancrofti" infected patients. These antibiotics, while acting through a slightly more indirect route, are promising antifilarial drugs.

Secondary bacterial infection is often observed with lymphatic filariasis. Rigorous hygiene practices, including washing with soap and water daily and disinfecting wounds can help heal infected surfaces, and slow and potentially reverse existing tissue damage. Promoting hygiene is essential for lymphatic filariasis patients given the compromised immune and damaged lymphatic systems and can help prevent suffering and disability.