• Two new and two known flavonoids were isolated from the thorns of Gleditsia sinensis . • The absolute configurations were deduced by interpretations of the ECD spectra. • The inhibition effects against the NRK 52e cells apoptosis induced by LPS were detected. Two new flavonoids, (2 R ,3 R ,7′′ R ,8′' S )-5′′-methoxyl-silychristin A, (2 R ,3 R ,7′′ S ,8′′ R )-5′′-methoxyl-silychristin A, and two known analogues were isolated from the thorns of Gleditsia sinensis . Their structures were determined by spectroscopic data analysis. The absolute configurations of the new compounds were deduced by interpretation of the ECD spectra. The cytoprotective effects of the isolated compounds against lipopolysaccharide (LPS)-induced apoptosis in normal rat kidney tubule epithelioid (NRK 52e) cells were investigated in vitro and the results showed that compounds 2 and 3 exhibited moderate protective effects with EC 50 values of 10.5 and 8.3 μM, respectively.