Pyrethrum is a natural mixture of six insecticidal esters, recognized for low mammalian toxicity and limited persistence in the environment. In this study, World Health Organization standard bioassays were used to evaluate the performance of pyrethrum against both susceptible and pyrethroid-resistant Anopheles gambiae s.s. The results showed that the intrinsic activity of pyrethrum was similar to that of permethrin but lower than that of deltamethrin against susceptible mosquitoes. However, pyrethrum was less affected by the presence of the kdr mutation than synthetic pyrethroids (with lower resistance ratios) and showed good knock-down effect, repellency, and blood-feeding inhibition against the pyrethroid-resistant strain. In laboratory condition, mosquito nets treated with 500–1,000 mg/m² (pyrethrum) remained effective, i.e., >80% mortality and/or >95% KD effect, for 9 mo. Conversely, the efficacy and residual activity of pyrethrum (Pynet 5% EC) on substrates was not conclusive, especially concerning mud, which is a porous substrate (mortality <80% after 3 mo at 2 g/m²). These findings suggested that pyrethrum may be a potential alternative candidate for the impregnation of mosquito nets and textiles in areas where resistance to pyrethroids has become problematic.