Nigella sativa (black seed) is widely recognized for its diverse pharmacological properties; however, its clinical application is often limited by poor bioavailability of key bioactive compounds such as thymoquinone. This study aimed to enhance the bioactive and antimicrobial efficacy of Nigella sativa from Northern Nigeria through nanoparticle formulation. Seeds and leaves were surveyed and collected from Borno, Yobe, and Kano states. Extracts were prepared and encapsulated using a solvent-evaporation/emulsification technique. Physicochemical properties, nutrient retention, antimicrobial activity, antioxidant capacity, and minimum inhibitory concentration (MIC) were evaluated. Nanoparticles demonstrated high encapsulation efficiency (77.5–83.4%) with particle sizes ranging from 140–185 nm and stable zeta potentials (–25.4 to –30.2 mV). Antibacterial and antifungal assays showed significantly larger inhibition zones for nanoparticle formulations compared to crude extracts. MIC values were reduced by approximately 50% following encapsulation. Antioxidant assays (DPPH, ABTS, FRAP) revealed lower IC₅₀ values for nanoparticles, indicating enhanced radical scavenging capacity. Kano-derived samples exhibited the strongest overall bioactivity, likely due to higher thymoquinone and saponin content. The findings demonstrate that nanoencapsulation significantly improves the antimicrobial and antioxidant performance of N. sativa, highlighting its potential for nutraceutical and pharmaceutical applications.