Background. Osteoarthritis (OA) is a chronic joint disease characterized by progressive degeneration of articular cartilage. It affects 20-25% of the population older than 45 years. The objective was to evaluate the effect of combining muscle strengthening exercises with the administration of oral type II undenatured collagen formulation (UC-II) in people with knee OA. Methods. A double-blind, placebo-controlled, randomized controlled trial with 60 patients with knee OA, randomly divided into the following groups: UC-II and physiotherapy group (CPG), placebo UC-II and physiotherapy group (PCPG), and physiotherapy group (PG). For groups using an oral type II undenatured collagen formulation, UC-II, 40 mg/day UC-II was administered for 90 days. Muscle strengthening exercises were associated with neuromuscular electrical stimulation (NMES), being performed three times a week for 30 days. At 30 and 90 days and six months after the intervention, the following were evaluated: pain, quality of life, functional capacity, muscle strength, and joint mobility. Results. Pain improved in all intervention groups, with no difference between groups. Quadriceps muscle strength increased in the CPG (p<0.005) and PG (p<0.05), the same being observed for active and passive knee flexion mobility (p<0.05). All groups decreased the TUG test execution time after 30 days (p<0.005 for the CPG and PG, and p<0.05 for the PCPG), but only the CPG and PG maintained the scores at 90-day and six-month assessments (p<0.005). Regarding the 6MWT, only the CPG increased the distance covered in all assessments (p<0.005). The PG traveled a greater distance than the PCPG at the 90-day assessment (p<0.05). The WOMAC score decreased significantly in all intervention groups. The Lequesne score decreased in all groups; however, the CPG and PG showed lower values at 30 days (p<0.005). Conclusions. Muscle strengthening exercises improved pain, mobility, strength, and function in knee OA patients. The association of UC-II seems to have accentuated the effect of exercise on this clinical improvement, especially in the long term.