The present work developed a virtual reality (VR) counterconditioning procedure (VRCP), and investigated its efficacy in treatment of cue-induced craving in individuals with methamphetamine (METH) dependence. In study 1, thirty-one patients diagnosed with METH dependence received VRCP, while twenty-nine METH-dependent patients in waiting-list group did not. In study 2, the VRCP was computerized as a VR treatment system. Six-hundred and twelve abstinent individuals with a history of METH dependence received the computerized VRCP, while two-hundred seventy-six abstinent individuals with a history of METH dependence in waiting-list group did not. Patients with METH dependence who received VRCP showed a significantly larger decrease on the score of METH-craving and METH-liking from baseline to follow-up assessments, compared to those who did not received VRCP. Participants received VRCP showed a significantly larger decrease in HRV indexes on time domain and non-linear domain from baseline to follow-up assessments during exposure to VR cues, compared to those in waiting-list group. These findings indicate that the counterconditioning procedure under VR environment may be a useful strategy in suppressing cue-induced reactivity for patients with METH dependence.