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Introduction: In addition to standard highly active antiretroviral therapy protocols, complementary therapies using natural compounds are widely used by human immunodeficiency virus (HIV)‐infected human patients. One such compound is the fermented wheat germ extract (FWGE), named Avemar. Materials and methods: In this study, we investigate the effects of Avemar in a feline‐acquired immunodeficiency syndrome model. MBM lymphoid cells were acutely infected by the American feline immunodeficiency virus (FIV)‐Petaluma (FIV‐Pet) and the European FIV Pisa‐M2 strains. FL‐4 lymphoid cells, continuously producing FIV‐Pet, served as a model for chronic infection. Crandell Rees feline kidney (CRFK) cells were infected by either FIV‐Pet or feline adenovirus (FeAdV) as a model for transactivation and opportunistic viral infection. Cell cultures were treated pre‐ and post‐infection with serial dilutions of spray‐dried FWGE (Avemar pulvis, AP), a standardized active ingredient in commercial Avemar products. Residual FIV and FeAdV infectivity was quantified. Results: In a concentration‐dependent manner, AP inhibited replication of FIV strains in MBM and CRFK cells by 3–5 log. Low AP concentration prevented FIV‐Pet release from FL‐4 cells. Higher concentrations destroyed virus‐producing cells with cytopathic effects resembling apoptosis. AP strongly inhibited FeAdV production inside CRFK cells but not in HeLa cells. Adenovirus particles are then released via the disintegration of CRFK cells. Discussion: This report is the first to describe the antiviral effects of Avemar. Further studies are required to confirm its in vitro and in vivo effects and to investigate the potential for its use as a nutraceutical in FIV‐infected felines or HIV‐infected humans. Conclusion: Avemar, as a single nutraceutical, inhibits FIV replication and destroys retrovirus carrier cells. An important conclusion is that prolonged Avemar treatment might reduce the number of retrovirus‐producing cells in the host. [ABSTRACT FROM AUTHOR]