Paclitaxel (PTX) is an anticancer drug that induces peripheral neuropathy-associated muscle weakness. However, only a few effective therapeutic agents are currently available. Shakuyakukanzoto (SKT) is a traditional kampo medicine that consists of two herbal medicines, Paeoniae radix (PR) and Glycyrrhizae radix (GR). SKT is used to treat muscle-related pain. Recently, we found that mice treated with PTX exhibited decreased grip strength. In the present study, we demonstrated that SKT attenuated the decrease in grip strength in mice treated with PTX. PTX was injected intraperitoneally once daily, every other day, a total of four times in mice. Dried water extract (WE)-SKT, WE-PR, and WE-GR were orally administered once a daily. PTX induced a reduction in grip strength. WE-SKT, but not WE-PR or WE-GR, inhibited the decrease in grip strength in PTX-treated mice. PTX decreased peripheral blood flow in mice. WE-SKT and WE-PR, but not WE-GR, inhibited the decrease in peripheral blood flow in PTX-treated mice. Histochemical staining showed that PTX induced skeletal muscle atrophy, whereas WE-SKT, but not WE-PR and WE-GR, inhibited atrophy. PTX reduced proliferation and F-actin formation in C2C12 cells. WE-SKT did not inhibit the above action of PTX in C2C12 cells. These results show that the direct action of PTX on skeletal muscles and PTX-induced muscle atrophy may be involved in the decrease in grip strength and peripheral blood flow. It is suggested that the improvement of these things by SKT contributes the inhibitory action of SKT on PTX-induced muscle weakness.