Objectives. To examine and investigate the efficacy of shea nut oil extract (SheaFlex75) in relation to knee osteoarthritis (OA). Methods. Thirty-three patients (age 63.6 ± 5.8 years) with knee OA were recruited. Real-time ultrasound imaging and surface electromyography were used to objectively assess the morphological changes and the activity of vastus medialis oblique (VMO) muscles during a 16-week intervention of SheaFlex75. The intraclass correlation coefficient (ICC) was calculated to examine the reliability of the interscans. A paired-sample t-test was used to compare the findings in different stages. The Spearman's rank correlation coefficient was used to examine the relationship between the relevant variables of OA and percentage of thickness change of VMO at different contraction levels. Results. The baseline findings showed strong correlation, suggesting that the reliability of interscans at pretest was high. The ability to contract the muscles of the knee to a 30% contraction level showed significant change between the baseline and after 16-week testing, both in terms of morphological changes and muscle activity. Pain scale reported a significant decrease at the 16th week. Conclusion. The results suggest that SheaFlex75 can relieve the symptoms of knee OA and can result in improvement of muscle control of the knee.