Paliurus spina-christi Mill., a member of the Rhamnaceae family, is a traditionally used medicinal plant in the management of a panoply of human ailments. The current research focused on its phytochemical profile and biological properties evaluated by its antioxidant and enzyme inhibitory properties. The methanol extract was found to be the most effective antioxidant as evidenced by its DPPH and ABTS scavenging activities, cupric and ferric reducing power (CUPRAC and FRAP), and high activity in phosphomolybdenum (PBD) assay, and also displayed the highest anti-tyrosinase activity. The n-hexane extract was the most effective AChE inhibitor (8.89 ± 0.08 mg GALAE/g) followed by the methanol (8.64 ± 0.01 mg GALAE/g) while the latter showed the highest BChE inhibition (2.50 ± 0.05 mg GALAE/g). Among the different solvent extracts of the stem, the methanolic extract showed highest antioxidant activity in the following assays: DPPH (909.88 ± 4.25 mg TE/g), ABTS (3358.33 ± 51.14 mg TE/g), CUPRAC (781.88 ± 16.37 mg TE/g), FRAP (996.70 ± 47.28 mg TE/g), and PBD (4.96 ± 0.26 mmol TE/g), while the dichloromethane extract showed the highest MCA (28.80 ± 0.32 mg EDTAE/g). The methanol extracts revealed the highest TPC and TFC among the different solvents used, and as for plant part, the stem extracts had the highest TPC ranging from 22.36 ± 0.26 to 121.78 ± 1.41 (mg GAE/g), while the leaf extracts showed the highest TFC ranging from 8.43 ± 0.03 to 75.36 ± 0.92 (mg RE/g). Our findings tend to provide additional scientific evidence on the biological and chemical activities of P. spina-christi, which may serve as a source of naturally occurring bioactive chemicals with potential biomedical applications.