Arthritis is mainly a geriatric disease that causes joint pain and lowers the quality of life. This clinical trial was performed to evaluate the efficacy of Lilium lancifolium Thunb. (HY-LL) in alleviating joint pain. Six candidate anti-inflammatory components including regaloside A were identified in HY-LL using HPLC analysis. All participants were assigned to the HY-LL or the placebo group and took tablets twice a day for 12 weeks. As a result, pain VAS and K-WOMAC total scores significantly decreased after 12 weeks compared to the baseline in the HY-LL group, with a statistically significant difference between the two groups (p = 0.043, 0.043). The K-WOMAC sub-scores for pain and function showed a statistically significant improvement in the HY-LL group compared to the placebo group (p = 0.023, 0.047). Furthermore, the participants’ overall quality of life improved after 12 weeks of HY-LL consumption (p = 0.024). However, no significant differences were observed in the blood biomarkers. Therefore, this study demonstrated the positive effect of 12 weeks of HY-LL consumption on joint pain and quality of life.