Artemisinin and its derivatives are widely recognized for their exceptional antimalarial efficacy. Recently, accumulating evidence indicates therapeutic potential beyond malaria. Despite these advances, detailed mechanisms and pharmacological limitations remain incompletely defined. This review summarizes their pharmacological activities and molecular mechanisms associated with oncology, immunoregulation, and metabolic disorders. Mechanistically, these compounds exert potent antitumor effects by inducing oxidative stress, arresting the cell cycle, triggering apoptosis, and inhibiting angiogenesis. They likewise modulate immune responses, re-establishing immune homeostasis and enhancing the effectiveness of immunotherapeutic strategies. Preliminary evidence also suggests involvement in metabolic regulation, pointing to promising avenues for treating metabolic disorders. Given alternative mechanisms of artemisinin and its derivatives, we also discuss the trinity modulation network among antitumor activity, immunoregulation, and metabolic homeostasis. We anticipate that future research will address these knowledge gaps, thereby enhancing the clinical utility of artemisinin and its derivatives and improving patient outcomes across diverse pathologies.