A green-lipped mussel (GLM) preparation was evaluated in a randomized, double-controlled and double-blinded clinical trial. It was hypothesized that the treatment effect would be less than that of the positive control (carprofen) but more than that of the negative control (placebo). Forty-five dogs with chronic pain and a radiographic diagnosis of osteoarthritis that were randomly allocated into one of three groups completed the study. All dogs were fed the test products or placebo for 8 weeks. The dogs were evaluated four times, at 4-week intervals. Six different variables were assessed: veterinary-assessed mobility index, two force plate variables, owner-evaluated chronic pain index and pain as well as locomotion visual analogue scales (VASs). Intake of extra carprofen was also evaluated. A chi-squared and a Mann–Whitney test were used to determine significance between groups. When changed to dichotomous variables, there were more dogs in the GLM than in the placebo group that improved, according to veterinary-assessed mobility, owner-evaluated chronic pain index and pain VAS (P = 0.031, P = 0.025, P = 0.011, respectively). For the same three, the odds ratio and their confidence interval were over one. The extent of improvement was significantly different between the GLM and the control in veterinary-assessed mobility (P = 0.012) and pain VAS (P = 0.004). In conclusion, GLM alleviated chronic orthopedic pain in dogs although it was not as effective as carprofen. As no side-effects were detected, GLM may be beneficial in dogs e.g. when non-steroidal anti-inflammatory drugs cannot be used.