Breast cancer remains highly prevalent due to its complex etiology. Curcumin, a natural compound with therapeutic potential, faces physicochemical limitations, leading to the development of its synthetic analog, pentagamavunon-6 (PGV-6). However, PGV-6's low aqueous solubility limits its efficacy, necessitating nanoliposome-based encapsulation to enhance its effectiveness. This study is aimed at synthesizing, characterizing, and evaluating the antioxidant and anticancer properties of PGV-6-loaded nanoliposome (NLP). The NLPs were fabricated using the thin film hydration technique which composed of LPC, cholesterol, Tween-80, and PGV-6 (28:4.3:7.8:1). The particle characterization was conducted by measuring particle size, polydispersity index (PDI), and zeta potential using PSA and observing their morphology using SEM and HR-TEM. Antioxidant activity was assessed using ABTS assay, while anticancer effects were evaluated through cytotoxicity, apoptosis, lysosomal uptake, ROS generation, and cell cycle assays on MCF-7 breast cancer cells. The NLP formed spherical nanoparticles with a mean particle size of 127.7 ± 1.75 nm, PDI of 0.2 ± 0.03, and zeta potential of - 7.8 ± 0.64 mV. The NLP enhanced the antioxidant activity of PGV-6 by 15.4-fold (IC 3.24 ppm) compared to free PGV-6 (IC 49.93 ppm). Additionally, the cytotoxicity of NLP against cancer cells was 2.6 times stronger (IC 9.75 ppm) than free PGV-6 (IC 25.40 ppm). Mechanistically, free PGV-6 induced apoptosis by inhibiting the cell cycle at the G2/M phase, whereas NLP triggered apoptosis through an intrinsic mechanism, not only via mitochondrial pathway but also by targeting lysosomes to elevate intracellular ROS production and initiate the caspase cascade via the lysosomal pathway. These findings demonstrate that nanoliposome encapsulation improves the therapeutic potential of PGV-6, supporting its promise as a more effective antioxidant and anticancer agent.