Glioma remains to be the severe disease to threaten the human health. The present study aims to determine the lipid profile alteration in the patients with glioma, and the influence of altered lipid components towards the activity of drug-metabolizing enzymes UDP-glucuronosyltransferases (UGTs). Serum samples were collected from the healthy volunteers and the patients with glioma. Lipidomics analysis showed the significant elevation of LPC18:0 and LPC18:1 in patients with glioma. The influence of lipid components LPC18: 0 and LPC 18:1 towards UDP-glucuronosyltransferases (UGTs) was investigated using recombinant UGTs-catalyzed 4-MU probe reaction, and the results showed that LPC18:0 and LPC18:1 activate the activity of UGT1A1, and inhibited the activity of UGT1A6 and UGT1A8. In conclusion, the present study used lipidomics analysis method to find the significant change of LPC18:0 and LPC18:1 in the patients with glioma. LPC18:0 and LPC18:1 were furtherly demonstrated to exert regulation effect towards UGT isoforms. It was demonstrated that altered lipid profile in glioma patients affects the activity of drug-metabolizing enzymes.