<p><i>Musca domestica</i> L. (Diptera: Muscidae) is predominantly a cosmopolitan insect in crowded human dwellings and a serious health hazard. The effects of entomopathogenic fungi species including <i>Beauveria bassiana</i> (Balsamo) Vuillemin (Hypocreales: Cordycipitaceae), <i>Metarhizium anisopliae</i> (Metschnikoff) Sorokin (Hypocreales: Clavicipitaceae) and <i>Cordyceps fumosorosea</i> (Wize) Kepler, B. Shrestha &amp; Spatafora (Hypocreales: Cordycipitaceae) isolates were evaluated on life history parameters and detoxification enzymes activities of <i>M. domestica</i> under laboratory conditions using LC₁₀, LC₃₀ and LC₅₀ concentrations. A concentration-dependent response was observed with entomopathogenic fungi significantly reducing adult longevity, fecundity, pupal weight and duration. However, the fungal application did not significantly affect the hatching percentage, larval duration, percent pupation, adult emergence and sex ratio of the progeny. Additionally, following fungal application, increased levels of total esterases, glutathione S-transferases, acid and alkaline phosphatases were observed. Interestingly, acetylcholinesterase activity was suppressed after fungal treatment. The current study provides information regarding mechanisms aiding <i>M. domestica</i> in withstanding fungal infection. Likewise, the study suggested that fungi could be used as an enzyme inhibitor as it suppressed acetylcholinesterase activity after fungal infection. This consideration may provide a basis for developing a biologically safe pest management solution.</p>