Background <p>Among adult population, the osteoarthritis (OA) of knee is the major issue that can lead to pain, functional limitations, and reduced quality of life. Exercise therapy is a core component of management, yet the added value of core stability training in conjunction with kinetic chain exercises remains underexplored.</p> Objective <p>To determine the effects of combined mode kinetic chain exercise with and without core stability training on pain, range of motion and quality of life in patients with knee OA.</p> Methods <p>A total of 48 patients with osteoarthritis in their knees were the subjects of a randomized controlled experiment at PSRD Hospital in Lahore were randomly allocated to either Group B (kinetic chain exercise only) or Group A (kinetic chain exercise with core stability training) with 24 participants each. For 12&#xa0;weeks, interventions were carried out three times a week. Quality of life (KOOS), knee range of motion (goniometry), and pain (NPRS) were evaluated at baseline, six weeks, and twelve weeks.</p> Results <p>Group A and B both groups showed significant improvements in NPRS, ROM, and KOOS scores over time (p &lt; 0.05). At 12&#xa0;weeks, Group A demonstrated a greater reduction in pain compared to Group B (p = 0.002). Flexion ROM improved by 19.6° ± 3.2° in Group A versus 12.4° ± 2.9° in Group B (p &lt; 0.001). KOOS total score increased by 34.8 ± 5.6 in Group A and 25.7 ± 5.1 in Group B (p &lt; 0.001).</p> Conclusion <p>Incorporating core stability exercises into a kinetic chain exercise program yields superior improvements in pain reduction, knee range of motion and quality of life in knee osteoarthritis patients compared to kinetic chain exercises alone.</p> Trial registration <p>The study was registered at Clinical trial.gov and was submitted on 2024–04-18. Trial Registry number was NCT06377813.</p>