For a long time, the ethnic minorities in Ninh Thuan province, Vietnam have mixed Coptosapelta tomentosa Rubiaceae with other types of medicinal herbs to create an esoteric remedy called “Cao Khai”. This study had provided scientific evidence on phytochemical screening and antioxidant potentials of diethyl ether, ethanol and aqueous extracts of “Cao Khai”. Phytochemical screening of crude “Cao Khai” extracts showed the presence of mutiple components such as saponins, flavonoids, volatile oils, triterpenoids, organic acids, anthraquinon, coumarin, reducing compounds and polyuronid. The polyphenols and flavonoids content were determined using gallic acid and quercetin as a standard, respectively. 1,1-diphenyl-2-picryl-hydrazyl (DPPH) and 2,2′–azino–bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) methods were used to measure free radical scavenging capacity. Results have shown that the total polyphenol and flavonoids content achieved 49.67 ± 0.35 µgGAE/mg and 5.49 ± 0.84 μgQE/mg, respectively. “Cao Khai” had low IC50 values of 126.06 ± 1.33 µg/mL (DPPH) and 35.4 ± 0.74 µg/mL (ABTS), which indicated that the crude drug “Cao Khai” illustrated significant free radical scavenging activity in a dose-dependent manner, as compared to ascorbic acid.