AIMS: This study aims to develop and evaluate oleuropein loaded surface functionalized folate-targeted - PEG liposomes for the effective management of prostate cancer in an animal model. MATERIALS AND METHODS: Film hydration-cum-extrusion technique was used to produce liposomes. Particle size, entrapment efficiency, drug loading, electron microscopy, and drug release study were performed for the characterization. Cell viability and various in vitro studies (phosphatidylserine internalization, TUNEL assay, measurement of mitochondrial membrane potential and caspase-3 assay) were performed to compare the anticancer and apoptotic effects of developed liposomes against the plain oleuropein. Comparative pharmacokinetic profiling and anticancer efficacy studies including a change in tumor volume, body weight, and survival analysis were performed in mice model. KEY FINDINGS: The developed liposomes (OL-FML) showed the particle size of 184.2 ± 9.16 nm, the zeta potential of 1.41 ± 0.24 mV, entrapment efficiency of 63.52 ± 4.15% and drug loading of 21.31 ± 2.37%. OL-FML showed higher in vitro anti-proliferative effect and apoptosis on 22Rv1 cells. In vivo pharmacokinetic study revealed a nearly 6 fold increase in the bioavailability of OL-FML (AUC = 641.78 ± 103.764 μg/mL·hr) as compared to OL solution (AUC = 104.11 ± 18.374 μg/mL·hr) in mice. Increased tumor suppression, weight loss resistance, and survival probability were observed in 22Rv1 induced tumor-bearing mice with OL-FML treatment as compared to OL. SIGNIFICANCE: The study provides conclusive evidence for the utilization of combining passive and active targeting strategy to enhance the anticancer effect of OL.