This study sought to evaluate the added advantage of mediating ZnO nanostructures with a medicinal plant. The synthesized ZnO nanocrystalline structures were confirmed by Fourier transform infrared spectrometer and characterized through scanning electron microscope, transmission electron microscope, ultraviolet–visible spectroscopy, and energy‐dispersive X‐ray spectrometer. The antioxidant, anti‐inflammatory, and antimicrobial activities of the ZnO nanostructure mediated with methanol extracts of the leaf, fruit, and seed of Chrysophyllum albidum were then evaluated using DPPH assay, egg albumin denaturation assay, and agar well diffusion methods, respectively. All the characterization analyses revealed high‐purity hexagonal‐shaped ZnO nanoparticles which were agglomerated. The mean diameter of the particles determined were 11.3 ± 1.7 nm, 20.4 ± 3.2 nm, and 27.3 ± 6.6 nm for C. albidum seed, fruit, and leaf extract‐mediated ZnO NPs, respectively. The EC50 values recorded for the antioxidant activity of the extract‐mediated ZnO NPs were 0.507 ± 0.015, 0.255 ± 0.006, 0.193 ± 0.003, and 0.004 ± 0.000 mg/mL for leaf, fruit, seed, and ascorbic acid, respectively. From the antimicrobial analysis, C. albidum seed extract‐mediated ZnO NPs recorded the highest zone of inhibition (24.33 ± 0.47) against S. aureus whereas C. albidum leaf extract‐mediated ZnO NPs gave the lowest zone of inhibition (13.00 ± 1.41) against E. coli at a concentration of 50 mg/mL. Moreover, C. albidum fruit extract‐mediated ZnO NPs presented the highest zone of inhibition (18.00 ± 0.82) against the fungus (C. albicans) also at a concentration of 50 mg/mL. The IC50 values recorded for the anti‐inflammatory activity of the extract‐mediated ZnO NPs showed inhibition in the order fruit > seed > leaf. Meanwhile, extracts of the samples showed the presence of flavonoids, alkaloids, saponins, and glycosides as phytochemical constituents in the leaf, fruit, and seed samples. In conclusion, the synthesized ZnO NPs from the extracts of C. albidum displayed significant antioxidant, anti‐inflammatory, and antimicrobial activities against some selected microbes and fungi.