Food-medicine homologous (FMH) plants have gained increasing interest due to their nutritional and therapeutic properties. Fatigue is a common health issue driven by physical and mental stress worldwide lacking efficient treatments. The significant anti-fatigue effects of FMH plants have attracted much attention with various active components including polysaccharides, flavonoids, and saponins and emerging compounds (such as macaenes and curcuminoids) demonstrating synergistic anti-fatigue effects. These ingredients could regulate energy metabolism, reduce oxidative stress, inhibit inflammatory pathways, and modulate the nervous system, thereby delaying fatigue onset and improving endurance. Notably, numerous research findings have been widely applied due to their efficacy in alleviating fatigue, identifying active components, exploring the action mechanism, and developing related products.. This review highlights the key active ingredients of FMH plants, summarizes the anti-fatigue mechanisms, discusses current applications and clinical evidence, which will provide insights for future research and functional development of FMH substances.