New antibabesial drugs are required to fight resistant parasites, and plant-derived natural products are a robust source. Six kinds of natural product extracts derived from herbal medicines that are traditionally used for the treatment of malaria were selected to test the antibabesial effect on Babesia gibsoni in vitro and in vivo. Parasitized blood was collected from dogs infected with B. gibsoni to evaluate the inhibitory effect of verbenalin, catechin hydrate, dihydrolycorine, embelin, ursolic acid, agrimol B, and bruceine H in vitro. The expression levels of the 18S rRNA gene in all drug-treated groups were determined by relative quantification using a real-time PCR method. Significant inhibition of the in vitro growth of B. gibsoni was observed after treatment by those natural product extracts (200 nM concentration) (P < 0.05). Catechin hydrate showed the highest activity in vitro due to the lowest expression levels of the 18S rRNA gene. The IC50 value of catechin hydrate against B. gibsoni was 273 nM. In B. gibsoni infected dogs, intravenous administrations of catechin hydrate and diminazene aceturate showed significant (P < 0.05) inhibition of B. gibsoni growth at a dose of 11 mg/kg and 10 mg/kg, respectively, compared to the control group. The results of our study may suggest that catechin hydrate may be a promising alternative to treat canine babesiosis caused by B. gibsoni.