Electrostatic spraying is recognized as a straightforward technique for the fabrication of polylactic acid (PLA) microspheres. PLA is notable for its biodegradability and versatile mechanical properties. Nonetheless, its limited cell affinity and the absence of active functional groups for drug interaction restrict its usage. In this study, we employed phosphoglyceride (P-P-Gly) coating to enhance the properties of PLA microspheres. The modified PLA microspheres underwent characterization through scanning electron microscopy (SEM), X-ray diffraction (XRD), and differential scanning calorimetry (DSC). The findings confirmed the successful coating of P-P-Gly onto the microspheres. The in vitro cytotoxicity of the modified PLA microspheres was assessed using the CCK-8 assay. The results demonstrated improved cell affinity for both modified and curcumin-loaded PLA microspheres. Notably, when the curcumin loading concentration in PLA microspheres reached 3 mg/mL, the cell viability of L-929 cells surged to 127%. PLA microspheres with lower concentrations of curcumin exhibited a proliferative effect on both L-929 cells and HUVECs. These findings suggest that PLA microspheres, when modified and loaded with curcumin, exhibit commendable biocompatibility, making them suitable for applications in tissue engineering.