<i>Plectranthus</i> species (Lamiaceae) have been employed in traditional medicine and this is now validated by the presence of bioactive abietane-type diterpenoids. Herein, sixteen <i>Plectranthus</i> acetonic extracts were prepared by ultrasound-assisted extraction and their biological activity was screened. The antimicrobial activity of each extract was screened against yeasts, and Gram-positive and Gram-negative bacteria. The <i>P. hadiensis</i> and <i>P. mutabilis</i> extracts possessed significant activity against <i>Staphylococcus aureus</i> and <i>Candida albicans</i> (microdilution method). Moreover, all extracts showed antioxidant activity using the DPPH method, with <i>P. hadiensis</i> and <i>P. mutabilis</i> extracts having the highest scavenging activities. Selected by the <i>Artemia salina</i> model, <i>P. hadiensis</i> and <i>P.ciliatus</i> possessed low micromolar anti-proliferative activities in human colon, breast, and lung cancer cell lines. Furthermore, the most bioactive extract of <i>P. hadiensis</i> leaves and the known abietane diterpene, 7α-acetoxy-6β-hydroxyroyleanone isolated from this plant, were tested against the aggressive type triple negative breast cancer (MDA-MB-231S). <i>P. hadiensis</i> extract reduced the viability of MDA-MB-231S cancer cell line cells, showing an IC₅₀ value of 25.6 µg/mL. The IC₅₀ value of 7α-acetoxy-6β-hydroxyroyleanone was 5.5 µM (2.15 µg/mL), suggesting that this lead molecule is a potential starting tool for the development of anti-cancer drugs.