Purpose: To compare the effects of reflexology and progressive muscle relaxation training for people with multiple sclerosis, provided by nurse therapists, on psychological and physical outcomes. Methods: A crossover design was chosen with a 4-week break between treatment phases. The Short Form 36 and General Health Questionnaire 28 were completed by patients (n = 50) pre and post each of the 6-week treatment phases. Salivary cortisol levels, State Anxiety Inventory, systolic and diastolic blood pressure and heart rate data were collected pre and post the weekly sessions. Results: All of the chosen measures except for three SF-36 scales recorded significant changes, however, despite the 4-week break (washout period), most outcome measures did not return to their pre-treatment baseline levels. This meant that the analysis of the data was complicated by significant effects involving ordering of treatment occurring for eight of the variables (one from SF-36, two from the GHQ, SAI, Salivary Cortisol, Systolic BP and HR). However, there was a difference in the State Anxiety Inventory values between the treatments of the order of 1.092 units (95%CI 0.211-1.976) (p = 0.016, Wilks λ = 0.885, df = 1, 48) in favour of reflexology. Changes in salivary cortisol comparing levels pre 1st to post 6th session favoured reflexology (95%CI 0.098-2.644) (p = 0.037, Wilks λ = 0.912, df = 1, 48). A significant difference was found in the way the treatments affected change in systolic blood pressure following sessions; this favoured progressive muscle relaxation training (p = 0.002, Wilks λ = 0.812, df = 1, 48). Conclusion: Positive effects of both treatments following sessions and over the 6 weeks of treatment are reported, with limited evidence of difference between the two treatments, complicated by ordering effects.