Calls for the cultivation of medicinal plants in Africa are growing louder due to their cultural, therapeutic, and economic value. However, due to the declining soil quality and environmental pollution (caused partly by the overuse of chemical fertilizers), overharvesting of wild populations and use of unsustainable agricultural practices negatively impact medicinal plants’ quality and yield. As such, biofertilizers can be an eco-friendly alternative by exploiting beneficial microorganisms like Rhizobacteria, Azotobacter, and Azospirillum in order to enhance nutrient availability, improve soil health, and stimulate plant growth and the biosynthesis of secondary metabolites critical for therapeutic efficacy. Nevertheless, their adoption by African smallholder farmers is still low, partly due to a lack of knowledge, limited access, and economic and policy barriers. In this chapter, we explore possible solutions to these challenges, such as farmer education and changes to policies, and mix them with various sustainable climate-smart agriculture. Incorporating biofertilizers in African medicinal plant production systems is significant for progressing towards attaining sustainability and climatic resilience.