Both dextromethorphan (DM) and IV lidocaine improve postoperative pain relief. In the present study, we evaluated the interaction of DM and IV lidocaine on pain management after laparoscopic cholecystectomy (LC). One-hundred ASA physical status I or II patients scheduled for LC were randomized into four equal groups to receive either: (a) chlorpheniramine maleate (CPM) intramuscular injection (IM) 20 mg and IV normal saline (N/S) (group C); (b) DM 40 mg IM and IV N/S (group DM); (c) CPM 20 mg IM and IV lidocaine 3 mg · kg−1 · h−1 (group L); or (d) DM 40 mg IM and IV lidocaine (group DM+L). All treatments were administered 30 min before skin incision. Analgesic effects were evaluated using visual analog scale pain scores at rest and during coughing, time to meperidine request, total meperidine consumption, and the time to first passage of flatus after surgery. Patients of the DM+L group exhibited the best pain relief and fastest recovery of bowel function among groups. Patients in the DM and L groups had significantly better pain relief than those in the C group. The results showed an additional effect on pain relief and a synergistic effect on recovery of bowel function when DM was combined with IV lidocaine after LC.