This study aimed to enhance the antibacterial efficacy of BBR, a natural alkaloid with limited bioavailability and solubility, by encapsulating it in niosomes using saponin as a biosurfactant. Niosomes, non-ionic surfactant-based vesicles, improve drug stability and targeted delivery. The niosomes were synthesized using a ball milling-assisted method to optimize particle size and encapsulation efficiency. The formulation was characterized for particle size, zeta potential, encapsulation efficiency, and release kinetics. Niosomes with saponin had a particle size of 185 nm, a negative zeta potential, and the slowest release rate, following the Higuchi model. BBR-loaded niosomes achieved impressive entrapment efficiency (E.E%) of up to 93.7. The addition of saponin was expected to boost the antibacterial effects through synergistic mechanisms. The antibacterial efficacy of the formulation was assessed against Staphylococcus aureus and Escherichia coli. The resulting niosomal formulation exhibited significantly improved antibacterial activity compared to free BBR. The minimum bactericidal concentration (MIC) of the niosomes containing saponin (NSa2) and BBR against S. aureus and E. coli was found to be 0.08 ± 0.0 mg/ml. In contrast, the MBC of BBR alone against S. aureus was 0.24 ± 0.02 mg/ml, while for E. coli, it was 0.25 ± 0.02 mg/ml. These findings suggest that this niosomal formulation could be a promising approach for delivering BBR with improved therapeutic efficiency.