Wei Kang Su (WKS) is a commercial herbal product based on a Chinese herbal formula, Shengmai San. Here, we investigated the effects of long-term treatment with WKS on mitochondrial antioxidant status and functional ability, as well as heat shock protein (Hsp) 25/70 production, in various tissues of rats. WKS treatment enhanced mitochondrial antioxidant status and ATP generation capacity, as well as Hsp 25/70 production in various rat tissues. WKS treatment suppressed plasma reactive oxygen metabolite levels and protected against carbon tetrachloride hepatotoxicity in rats. Long-term WKS treatment may prevent diseases by enhancing the resistance of mitochondria to oxidative stress.