In this study, folic acid-conjugated lipid nanoparticles were successfully prepared to enhance the active targeting of capsaicin (CAP) in ovarian cancers. The particles were nanosized and exhibited a controlled release of drug in the physiological conditions. The folic acid (FA)-conjugated system exhibited a remarkably higher uptake of nanoparticles in the cancer cells compared to that of non-targeted system. The folate-conjugated CAP-loaded lipid nanoparticles (CFLN) upon interacting with cancer cells were internalized via receptor-mediated endocytosis mechanism and resulted in higher concentration in the cancer cells. Consistently, CFLN showed a remarkably higher toxic effect compared to that of non-targeted nanoparticle system. CFLN showed significantly higher cancer cell apoptosis with nearly 39% of cells in apoptosis chamber (early and late) compared to only ∼21% and ∼11% for CAP-loaded lipid nanoparticles (CLN) and CAP. The loading of drug in the lipid nanoparticle system extended the drug retention in the blood circulation and allowed the active targeting to specific cancer cells. The prolonged circulation of drug attributed to the antifouling property of polyethylene glycol molecule in the structure. Overall, study highlights that using targeting moiety could enhance the therapeutic response of nanomedicines in the treatment of solid tumors.