In this report, the PTP1B inhibitory effect of Calystegia soldanella was investigated. Bioassay-guided fractionation of the crude extracts revealed that the n-hexane fraction had the strongest PTP1B inhibitory effect. Nine known alkyl p-coumarates were isolated from the n-hexane fraction, and each compound was evaluated for its effect on PTP1B. All compounds effectively inhibited PTP1B activity. The IC50 values of the compounds were 3 (10.8 μg/mL) > 2 (15.5 μg/mL) > 7 (26.6 μg/mL) > 1 (37.0 μg/mL) > 8 (41.2 μg/mL) > 9 (43.4 μg/mL) > 5 (44.7 μg/mL) > 4 (> 50 μg/mL) > 6 (> 50 μg/mL).