<p>In this study, a biodegradable nanocomposite composed of polyhydroxybutyrate-co-chitosan and cobalt oxide (PHB-co-CS/Co₃O₄) was developed for targeted and sustained in-vitro release of curcumin (CUR). The nanocomposite was prepared by varying the concentrations of Co₃O₄ nanoparticles (NPs) and using chitosan with different molecular weights (LCS, HCS) to optimize the release profile. The PHB-co-CS copolymer was synthesized through a coupling reaction between PHB-diol and the terminal isocyanate groups of chitosan, using stannous octanoate as a catalyst. PHB-diol was obtained via transesterification of PHB with ethylene glycol. Amine group in CS was protected by phthalic anhydrides followed by reaction with hexamethylene diisocyanato. Co₃O₄ NPs were synthesized by reacting cobalt acetate with sodium carbonate in ethylene glycol. CUR was first loaded onto the Co₃O₄ NPs and then dispersed within the PHB-co-CS copolymer matrix. Structural and chemical characterization was performed using X-ray diffraction (XRD) and Fourier transform infrared (FTIR) spectroscopy. In-vitro release studies were conducted in buffer solutions at pH 5.4 and 7.4, showing enhanced release in acidic conditions, which supports tumor-specific targeting. Formulations with lower molecular weight chitosan released curcumin more rapidly. Among the tested systems, the PHB-co-LCS/10%CUR@Co₃O₄ nanocomposite exhibited the strongest anticancer effect, with IC₅₀ of 29.1&#xa0;µg/mL against HCT-116 colorectal cancer cells. These results highlight the promise of combining green materials and sustainable approaches to develop effective, targeted drug delivery platforms for cancer treatment.</p>