The color and quality of edible and medical honeysuckle will be affected by the environment condition such as light, temperature, and humidity during storage. In this study, taking temperature and humidity as an example, the changes of color and quality of honeysuckle at 25 °C and 75% relative humidity conditions were clarified through accelerated tests, and the change mechanism was explored. The results showed that after 18 days of storage, the color changed from green-white to brown, and the color parameter showed that a* value increased by 2.10 times, and L* and h* value decreased by 4.34% and 10.14%, respectively. The contents of chlorophyll a and carotenoid decreased by 33.92% and 34.87%, respectively. Total phenol content decreased by 39.85% while total flavonoid content increased by 10.54%. The antioxidant activities of the three methods decreased by 47.85%, 7.84% and 68.02%, respectively. The peroxidase (POD) and polyphenol oxidase (PPO) activities after 18 days were higher than those before storage. Chlorogenic acid content significantly decreased, suggesting a gradual deterioration in quality. According to untargeted metabolomics analysis, 74 differential metabolites related to these changes were screened and identified, including chlorophyllide a for chlorophyll degradation and 5-hydroxymethylfurfural for Maillard reaction. Combined with KEGG pathway analysis, it was found that the browning and quality decrease were caused by the enzymatic reaction induced by PPO and POD and the non-enzymatic Maillard reaction. In summary, this systematically explains the Chinese Pharmacopoeia describes the character of honeysuckle as “gradually darkening on keeping”.