Abstract: To reduce the waste of resources, kiwifruit residue was fermented by Lactobacillus plantarum to prepare the beverage. The effects of solid-liquid ratio, inoculation volume, initial TSS and fermentation time on sensory score and viable count of the product were investigated by single-factor experiments. On these grounds, the fermentation process was optimized by response surface methodology with the sensory score as the response value. Furthermore, the changes in its nutritional quality, antioxidant activity and flavor during fermentation were analyzed. Results showed that, the optimal fermentation process of kiwifruit residue beverage was as follows: Initial TSS 12.4%, inoculation volume 3.3%, fermentation time 36 h, and the sensory score of the product was 87.17 scores. The nutritional quality assay showed that, as time fermentation, the viable count and the contents of soluble protein and total acid increased, total phenol content initially decreased and then increased, flavonoids content had no significant difference, and the contents of total sugar and ascorbic acid decreased. Under the optimum process, ABTS⁺· scavenging rate, DPPH· scavenging rate as well as iron reduction increased by 9.59%, 6.89%, and 4.08%, respectively. After 36 h fermentation, the product reached the best comprehensive nutritional quality. In addition, the assay of headspace-gas chromatography-ion mobility spectroscopy (HS-GC-IMS) showed that the first 24 h of fermentation was the transformation stage of flavor compounds, and 36 h was an important node in the flavor formation, while the compounds with pungent odor were over-accumulated after 48 h fermentation. Among them, the relative contents of ketones and esters increased, while the relative contents of aldehydes and alcohols decreased. Further study found that, during fermentation, the fruit aroma and caramel aroma decreased first and then increased, the fermentation aroma increased, and the characteristic aroma as well as green aroma decreased. The olfactory sensory score (31.00) was the highest at 36 h, and the main aroma changed from green aroma to fermented aroma. To sum up, the product under the optimal process conditions (fermentation 36 h) had excellent sensory and was rich in nutrition and flavor, while the fermentation process had a great impact on the overall quality of the product and was required to be strictly controlled.