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Natural products have acquired prominence in scientific study and medicine owing to their increasing significance in the treatment of human ailments. Manihot esculenta Crantz (cassava) is a fundamental agricultural food crop, widely utilized for its starchy tubers. Cassava leaves are rich in essential components such as calcium, iron, protein, and vitamins A, B, C and K. The leaves have several secondary metabolites, including alkaloids, tannins, and flavonoids, which exhibit anti-inflammatory, antibacterial, anti-diabetic, and immune-modulatory properties. These secondary metabolites may safeguard cells against oxidative stress, chronic diseases, viral ailments, cardiovascular conditions, and specific cancer kinds. These bioactive compounds play a vital role in mitigating oxidative stress, chronic inflammation, and immune dysregulation-key factors implicated in cancer initiation and progression-thus warranting comprehensive investigation of cassava leaves within this framework. Despite their rich phytochemical composition, the nutritional and medicinal significance of cassava leaves remains underexplored. This review aims to summarize the phytochemical constituents of cassava leaves and elucidate their potential health-promoting translational values and anticancer properties. By integrating in vitro, in vivo, and clinical evidence, the review highlights the molecular mechanisms of cassava leaf phytochemicals underlying their anticancer effects and discusses translational implications, existing research gaps, and future directions for experimental and clinical studies.