Uterine fibroids (leiomyomas) are common benign tumors that adversely affect women’s reproductive health, often causing heavy menstrual bleeding, pelvic pain, and infertility. Although their exact cause remains unclear, hormonal imbalances and oxidative stress are recognized contributors. Due to the limitations and side effects of conventional treatments, there is growing interest in alternative therapies, particularly medicinal plants. This study evaluates the antioxidant activity and phytochemical composition of two South African plants traditionally used to manage uterine fibroids: Gunnera perpensa (Ugobho) and Albizia tanganyicensis (Mphaphama). Phytochemical screening, thin-layer chromatography (TLC), 2,2-diphenyl-1-picrylhydrazyl (DPPH) assays, and Fourier-transform infrared spectroscopy (FTIR) were employed to analyze the extracts. The results revealed the presence of key bioactive compounds, including flavonoids, phenolic compounds, and tannins, which are associated with antioxidant and anti-inflammatory activities. Quantitative analysis showed that G. perpensa had the highest total phenolic content (87.87 ± 0.056 mg GAE/g DW) and total flavonoid content (56.38 ± 0.036 mg QE/g DW), followed by the AGMix formulation and A. tanganyicensis. In antioxidant assays, G. perpensa demonstrated the strongest DPPH radical scavenging activity (IC₅₀ = 3.45 μg/mL), while AGMix showed moderate activity (IC₅₀ = 7.98 μg/mL) and A. tanganyicensis displayed weaker activity (IC₅₀ > 20 μg/mL). FTIR analysis supported the presence of functional groups linked to antioxidant properties. These findings support the traditional use of G. perpensa and A. tanganyicensis for fibroid-related symptoms and provide a scientific rationale for their further development as natural therapeutic agents. Future research should aim to isolate and characterize the active compounds and evaluate their pharmacological effects.