Background: This study investigated the hepatic, renal and endogenous antioxidant status modulatory effects of chronic cosupplementation of rooibos and red palm oil (RPO) in male Wistar rats. Materials and Methods: Rats were randomized into four groups (n=10/group) and fed daily either standard rat chow (SRC) and water (Group I), SRC and the aqueous rooibos extract (2% w/v; Group II), SRC and RPO (200 µL/day) with water (Group III), or SRC and RPO (200 µL/day) with rooibos (2% w/v; Group IV) for 22 weeks. Results: Chronic feeding of rooibos, RPO or their combination did not induce any adverse hepatic or renal effects, as shown by serum levels of alkaline phosphatase, alanine-and aspartate aminotransferase, lactate dehydrogenase, albumin, creatinine, blood urea nitrogen and uric acid. Histopathology analyses showed that liver from the three supplementation groups displayed normal hepatic histoarchitecture. Chronic feeding of RPO did not influence the redox status in the blood and liver significantly. Supplementation of rooibos alone for 22 weeks significantly (P<0.05) increased the reduced glutathione (GSH) level, GSH/GSSG ratio and catalase (CAT) activity in the liver. Co-supplementation of rooibos and RPO significantly (P<0.05) increased plasma total polyphenol content, trolox equivalent antioxidant capacity (TEAC), as well as blood GSH and GSH/GSSG ratio. Plasma conjugated dienes (CD) and hepatic malondialdehyde (MDA) levels were reduced significantly by the combination treatment, which also increased significantly the activity of CAT, glutathione reductase (GR), as well as the GSH/GSSG ratio in the liver. Conclusion: Our results suggest that chronic feeding of an aqueous fermented rooibos extract alone or in combination with RPO modulate the endogenous antioxidant system in rats. This modulation could be indicative of a threshold effect and/or an additive effect indicating a positive interaction between the bioactive components in the rooibos and RPO; however future studies are needed to elucidate the nature and specific mechanisms involved. Also, the health status of the individual/experimental animal should be considered before antioxidant supplementation, as it is suggested to affect the outcome.