The African boxthorn (Lycium ferocissimum) is a medicinal plant belonging to the Solanaceae family that is used in traditional pharmacopeia. Here, its biological potential was assessed by analyzing the essential oil from its leaves (EOLF), extracted by hydro-distillation and major terpenes characterized by gas chromatography coupled to mass spectrometry (GC-MS). GC-MS analysis of EOLF identified fourteen compounds representing 99.95% of the total mass, which was dominated by carvacrol (35.96%) and sabinene (17.06%). EOLF exhibited antioxidant activity as characterized by several assays, including 2,2-diphenyl-1-picrylhydrazyl (DPPH), Ferric Reducing Antioxidant Power (FRAP), Total Antioxidant Capacity (TAC) and the β-carotene/linoleic acid test. According to the results obtained, EOLF exhibited antioxidant activity, as measured by the DPPH assay, with a mean IC₅₀ of 96 µg/mL, which is relatively close to that of quercetin (74 µg/mL) and BHT (49.16 µg/mL). Furthermore, the activity assessed using the FRAP method showed an EC₅₀ of 282 µg/mL, comparable to that of BHT (292 µg/mL). Based on the results of the TAC method, the antioxidant activity was 880 ± 4 µg AAE/mg, while the efficacy for inhibition of β-carotene was 80%. Effective antimicrobial activity against several bacterial and fungal strains was assessed by measuring inhibition zones and Minimum Inhibitory Concentrations (MICs). EOLF exhibited significant antimicrobial activity, particularly against Klebsiella pneumoniae, with an inhibition zone of 25.08 ± 0.93 mm and an MIC of 15.68 ± 0.83 µg/mL. For Staphylococcus aureus, an inhibition zone of 23.84 ± 0.88 mm and an MIC of 11.03 ± 0.27 µg/mL were recorded. Strong antifungal activity was also observed against Candida albicans, with an inhibition zone of 22.55 ± 0.87 mm and an MIC of 10.51 ± 0.47 µg/mL. The conducted in-silico analysis confirmed the affinity of the main compounds with key biological targets, suggesting their likely roles in the observed antimicrobial effects. The ADEM-Tox properties demonstrated that the analyzed compounds would only be lethal at very great concentrations, indicating low acute toxicity, and would not be expected to elicit toxic effects at therapeutic doses.