The ent-kaurane diterpenoid chepraecoxin A (CA) obtained in our previous study showed a potential inhibitory activity on α-glucosidase (IC<sub>50</sub> 274.5 ± 12.5 μM). In order to figure out the structure-activity relationships (SARs), twenty-two derivatives of chepraecoxin A were synthesized by modifying the ester, allyl, double bond and carboxyl groups, and assayed for their α-glucosidase inhibitory activity. Of them, eight compounds (14-17, 19-22) significantly increased activity with IC<sub>50</sub> values ranging from 16.1 to 71.4 μM, even higher than the positive control, acarbose (IC<sub>50</sub> 130.3 μM). Especially, compounds 17, 19 and 21 could inhibit α-glucosidase with IC<sub>50</sub> values of 16.9 ± 3.4, 16.1 ± 1.2, and 17.1 ± 0.6 μM, 17-fold higher than CA. The most active compound 19 was proven to be a non-competitive inhibitor with a K<sub>i</sub> value of 19.4 μM based on enzyme kinetics study. The primary SARs of CA derivatives were summarized for exploring antidiabetic candidates.