This study was designed as a double-blind randomized placebo-controlled study. The aim of this study was to evaluate the effects of high-intensity laser therapy (HILT) on pain, range of motion, function, muscle strength, and femoral cartilage thickness in patients with knee osteoarthritis. Sixty patients who were admitted between November 2021 and April 2022 and diagnosed with knee osteoarthritis based on anamnesis, physical examination, and imaging methods were included in the study. The patients observed during the research were randomly divided into two groups with 30 patients in each group. Hotpack, transcutaneous electrical nerve stimulation (TENS), exercise (5 days a week for a total of 15 sessions), and HILT (analgesic mode with a power of 10.0 w, energy density of 12 j/cm, and 2 min for every 25 cm, biostimulant mode with a power of 5.0 W, energy density of 120 j/cm, and 10 min for each 25 cm; total 9 sessions 3 days a week) were applied for 3 weeks for the first group, and hot pack, TENS, exercise (5 days a week for a total of 15 sessions), and sham laser treatment (0 W total 9 sessions 3 days a week) was applied for 3 weeks for the second group. The patients were evaluated with the determined scales before the treatment, at the end of the treatment, and at the third month. A goniometer was used to measure joint range of motion measurement, a visual analog scale (VAS) for pain, WOMAC Osteoarthritis Index to assess pain and function, Biodex System 3 isokinetic device for knee flexion-extension muscle strength measurement, and ultrasonography to measure femoral cartilage thickness. There was no statistically significant difference in VAS, range of motion, WOMAC, muscle strength, and femoral cartilage thickness measurement between the groups, whether before treatment, after treatment or at the third-month follow-up (p > 0.05). There was a statistically significant decrease in pain intensity, an increase in flexion range of motion, WOMAC, and femoral cartilage thickness in both groups (p < 0.005). A statistically significant increase was found in the average peak torque flexion muscle strength measurements at isokinetic 60°/s angular velocities in the post-treatment and third-month checkup compared to the pre-treatment analysis in both groups (p < 0.05). In conclusion, there was no statistically significant difference between HILT + exercise and placebo laser + exercise observed. However, the exercise program performed under the supervision of a physiotherapist has been shown to be effective in improving all parameters.