This review examines Aymara traditional medicine, which is deeply rooted in cultural perceptions of health and disease, and its utilization of medicinal plants rich in secondary metabolites-such as flavonoids, alkaloids, and saponins-to support immune function, emphasizing the synergy between ancestral knowledge and modern scientific research. Adhering to PRISMA 2020 guidelines, this review incorporates empirical studies from 2013 to 2024 on secondary metabolites and Aymara medicine, with a focus on the immunomodulatory effects of plants, while excluding non-indexed or irrelevant studies. Potential limitations include publication bias and reliance on secondary data. Three key plant genera-Azorella, Centaurium, and Amaranthus-were identified for their traditional medicinal uses, highlighting their pharmacological benefits, such as anti-inflammatory, antioxidant, and hepatoprotective effects. Specifically, xanthones, a class of secondary metabolites found in Centaurium, exhibit notable antioxidant, anti-inflammatory, antitumoral, and cardioprotective properties, which support their traditional use in treating hypertension and related ailments. Centaurium spp. is characterized by its bioactive compounds (secoiridoids, flavonoids, phenolic acids, and xanthones), offering valuable immunomodulatory, anti-inflammatory, digestive, and antimicrobial properties recognized in both scientific and traditional Aymara medicine for treating diseases and maintaining physical and spiritual balance. Overall, the study of secondary metabolites in Andean medicinal plants like Azorella, Centaurium, and Amaranthus underscores their diverse bioactive compounds with pharmacological properties, highlighting the Aymara community's integration of traditional and modern medicine through holistic practices that promote health, balance, and resilience against disease, while emphasizing the potential of these practices to enhance contemporary healthcare.