Osteoarthritis is one of the most common locomotor diseases, with a steadily increasing prevalence and incidence. Loxacon® is a food supplement capsule containing vitamins, minerals, and herbal extracts with Boswellia serrata extract and Harpagophytum procumbens extract as its two main active components. The study involved 88 patients at 4 sites. The 88 patients were divided into 3 groups. The first group received physical therapy and Loxacon® capsules for 5 weeks, while the second group (30 patients) received physical therapy only for 5 weeks, and the third group (30 patients) received physical therapy and placebo capsules for 5 weeks. After 5 weeks, physical therapy was discontinued in all three groups and all groups continued Loxacon® capsules exclusively for an additional 60 days. Physical therapy had been carried out by a standard protocol over 5 weeks. Investigated parameters included Western Ontario and McMaster Universities Arthritis Index (WOMAC) testing, European Quality of Life (EQ-5D-5L) quality of life test and the Range of Motion (ROM). Among the 4 visual analogue scale (VAS) values investigated from WOMAC, significant change was seen for functionality in all three groups; however, the extent of change was twice as large in the physical therapy + Loxacon® group at Visit 2 in comparison with the other two groups. In the physical therapy + placebo group, improvement was seen only at the 3rd visit when they were also receiving Loxacon® capsules. The most pronounced difference was seen in the minimum clinically important difference index, calculated from the quality of life-VAS, where those taking Loxacon® capsules had a chance 3 times as high to obtain clinical improvement versus the other two groups. Our study confirmed that a combination of boswellic acid and harpagosides is beneficial as an additional therapy in knee OA.