This study is aimed at providing a critical review of the botany, biological activities and medicinal uses of P. prunelloides. Documented information on botany, biological activities, and medicinal uses of P. prunelloides was collected from several online sources which included BMC, Scopus, SciFinder, Google Scholar, Science Direct, Elsevier, PubMed, and Web of Science. Additional information on the botany, biological activities, and medicinal uses of P. prunelloides was gathered from book chapters, books, journal articles, theses, and scientific publications sourced from the University of Fort Hare Library. The study showed that the leaves and roots of P. prunelloides are used as herbal medicines for bodily pains, burns, cancer, diabetes, fever, gastrointestinal problems, heartburn, heart problems, respiratory problems, retained placenta, rheumatism, sexually transmitted infections, skin infections, snakebite, sores, wounds, toothache, and vomiting. Pharmacological research revealed that P. prunelloides extracts have antibacterial, antimycobacterial, antifungal, antiviral, antidiabetic, anti-inflammatory, analgesic, antioxidant, uterotonic and cytotoxicity activities. Future studies should focus on evaluating the phytochemical, pharmacological, and toxicological activities of P. prunelloides crude extracts as well as chemical compounds isolated from the species.