Osteoarthritis (OA) is a degenerative joint disease frequently associated with obesity, which elevates proinflammatory cytokines such as interleukin-1β (IL-1β) and exacerbates joint degeneration. Obesity, defined clinically as a body mass index above 30 kg/m², continues to rise globally due to high-calorie diets, sedentary lifestyles, and low public awareness of healthy habits. In Southeast Asia, including Indonesia, Malaysia, Brunei, and Singapore, the prevalence of obesity reaches an average of 23.4%, with Indonesia reporting 35.5% of adults, 20% of children aged 5–12 years, and 14.8% of adolescents aged 13–18 years as overweight or obese. Halofuginone, a potential anti-inflammatory agent, has been suggested to modulate IL-1β levels and influence OA progression. This study aimed to analyze and determine the effect of Halofuginone administration on IL-1β levels in obese rat models with OA. An experimental study was conducted using obese rats induced with OA, divided into control and treatment groups, with the latter receiving Halofuginone. IL-1β levels were quantified using enzyme-linked immunosorbent assay (ELISA), and statistical analyses were performed to compare the groups. Results indicated that Halofuginone administration significantly reduced IL-1β levels in the treatment group compared to the control group, demonstrating its modulatory effect on inflammatory responses in obese OA models. These findings provide novel evidence of Halofuginone’s role in obesity-related OA, highlighting its potential translational application as a targeted anti-inflammatory therapy. The study contributes to future research directions on cytokine modulation and OA management, offering insights into therapeutic strategies to mitigate inflammation-driven joint degeneration in obese populations.