Abstract: Objective To investigate the effects of invisible functional appliances and twin-block appliances on the periodontal index and inflammatory factors in gingival crevicular fluid of adolescent orthodontic patients using enzyme-linked mmunosorbent assay (ELISA). Methods A total of 60 adolescent patients who were admitted to the Affiliated Hospital of Xuzhou Medical University with Class Ⅱ malocclusion (mean age 11.63±2.01 years) were included in the study. They were randomly divided into two groups (n=30). The research group was treated with invisible functional appliances, while the control group was treated with twin-block appliances. Their clinical efficacy, gingival index, and gingival bleeding index were compared at baseline, 3 months, and 6 months, and the concentrations of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in gingival crevicular fluid were measured. Results There were no statistical differences in sex, age, or periodontal index between the two groups at baseline (P>0.05), and clinical efficacy was comparable. After 3 months of treatment, the periodontal index in the twin-block appliance group increased compared to baseline (P<0.05). After 6 months of treatment, the periodontal index in this group was significantly higher than in the invisible functional appliance group (P<0.05). Moreover, after 3 months of treatment, IL-1β and TNF-α levels in the gingival crevicular fluid significantly increased in the twin-block appliance group (P<0.05). The invisible functional appliance group showed better periodontal health and lower inflammatory cytokine levels than the twin-block appliance group. Conclusions Invisible functional appliances are more beneficial for periodontal health during orthodontic treatment compared to twin-block appliances.