The harmful side effects associated with conventional anti-inflammatory pharmaceuticals has focussed attention on medicinal plants as alternative therapeutics. However, the use of medicinal plants is predominantly based on ethnobotanical knowledge and often lacks toxicity data and safety validation. A comprehensive review of the toxicity and phytochemical properties of southern African medicinal plants used for inflammation and pain-related ailments was undertaken. Various ethnobotanical books and search engines including Science direct, Sci-Finder, Google Scholar and Scopus were used to determine which medicinal plants have been screened for toxicity. A total of 117 medicinal plants have previously been evaluated by toxicity screening. The predominant toxicity test used was the MTT reduction assay (109 species), followed by the brine shrimp lethality assay (57 species), and the XTT assay (24 species). The Ames test, which was used to screen 20 species, was the most frequently used assay to determine mutagenic properties of the plant extracts. The top five most commonly screened cell lines were Vero monkey kidney cells (46 plant extracts), RAW 264.7 macrophages (23 extracts), human breast cancer cells (MCF-7, 12) (21 extracts), mouse fibroblast (3T3) (18 extracts) and Graham cells (HEK-293) (17 extracts). Over 80% of the tested medicinal plant extracts were found to be non-toxic. Although many species have been evaluated for their toxicity properties, plant extracts are often tested using one or two assays and also lack diversity in terms of choice of cell lines used for screening. Phytochemical studies remain scarce and substantial further work is required.