The increasing global population is putting more pressure on the livestock sector to enhance productivity and utilize agro-industrial waste effectively. The agro-industrial sector worldwide produces a significant number of byproducts, and their improper disposal contributes to environmental pollution. Nevertheless, these byproducts contain valuable bioactive compounds that offer potential health benefits. One of these fruits is guava (Psidium guajava), which is widely cultivated in humid and subtropical regions. Guava cultivation produces a significant amount of leaf waste, posing an environmental challenge. Enhancing the valorization of guava leaves (GL) can greatly improve sustainability and reduce environmental impact. The pharmacological properties of GL are well-documented, largely due to their rich concentrations of flavonoids, phenolic acids, triterpenoids, and tannins. This article presents a novel perspective on the immune-modulating and health benefits of GL or its extracts (GLE) as observed in animal studies. They possess a diverse range of biological activities, including antioxidants, anti-flu, anti-cough, anti-inflammatory, hepatoprotective, antimicrobial, and antidiarrheal properties. Incorporating animal diets with GL or GLE enhanced growth, blood health biomarkers, improved antioxidant status, immune function, and organ histology structure. Research indicates that dietary supplementation with 1.5% GL or 200mg/kg GLE significantly improves fish health by enhancing growth performance, strengthening immune responses, and increasing resistance against stressors and pathogens such as Aeromonas hydrophila, and Cypermethrin. This review emphasizes the beneficial role of GL and GLE as dietary supplements for animals and fish. This is attributed to their rich phenolic compound profile and related biological activities. Future research is crucial to fully elucidate their efficacy as feed supplements, further promoting sustainability in the livestock sector.