Here, milk protein casein was used as a reducing and capping agent for the biogenic synthesis of zinc oxide nanoparticles (ZnONP_CS) with a mean size of ∼9.2 nm. Further, its nanoconjugate with curcumin (ZnONP_CS–Cur) with a mean size of 13.7 nm was prepared. ZnONP_CS demonstrated excellent loading of curcumin, a popularly known anticancer phytochemical, with a loading capacity of 302.2 mg g⁻¹ and pH driven drug release up to 90% at pH 5.0. When applied in cancer cells, ZnONP_CS–Cur demonstrated higher cytotoxicity to multiple cancer cell lines (breast, cervical, osteosarcoma and myeloma) than ZnONP_CS or curcumin alone. We further observed that ZnONP_CS could induce intracellular reactive oxygen species, thus causing cytotoxicity in cancer cells. We also observed that this cytotoxicity induced by ZnONP_CS–Cur can be enhanced ∼10% further using folate receptor-based targeting. Moreover, ZnONP_CS–Cur demonstrated an enhanced anti-inflammatory activity of curcumin in RAW 246.7 cells. Both formulations exhibited excellent cytocompatibility to human keratinocyte and erythrocyte cells. Overall, we conclude that the ZnONP_CS and curcumin nanoconjugate can demonstrate high anticancer and anti-inflammatory activity in vitro, and thus can be considered as a possible therapeutic nanoconjugate for future treatment of cancer.