The objective of this study was to determine whether meditation affects pain and quality of life in people with multiple sclerosis (MS) and peripheral neuropathy (PN). A total of 22 patients (10 with MS, 12 with PN) participated in a weekly meditation class over a 2-month period. A total of 18 controls (7 with MS, 11 with PN) received standard care. Primary outcome assessments were based on the 36-item Short Form Health Status Survey (SF-36) and a visual analogue scale (VAS) for pain at baseline and at 2 months. Secondary outcome measures included the Neuropathy Impairment Score (NIS) for PN patients and the Patient-Determined Disease Steps (PDDS) questionnaire and 5-item Modified Fatigue Impact Scale (MFIS-5) for MS patients. After 2 months, study participants who practiced meditation reported an improvement in pain on the VAS (P = .035 combined group), summed physical health scores on the SF-36 (P = .011 MS, P = .014 PN), summed mental health scores (P = .02 combined group), vitality (P = .005 combined group), and physical role (P = .003 combined group). A significant improvement was also observed for bodily pain (P = .031) in MS patients. In contrast, no significant differences before and after the intervention were observed for controls. Regarding the secondary measure of fatigue, improved scores for the cognitive and psychosocial components of the MFIS were noted in MS patients in the intervention group (P = .037, P = .032). No statistically significant changes were observed in the NIS for PN patients or in PDDS scores for MS patients. Meditation may be helpful in reducing pain and improving quality of life in patients with MS and PN. The lack of changes seen in mobility (MS) and sensorimotor deficits (PN) suggests that meditation may not affect the overall clinical course.