Objective. To explore the clinical effect and aesthetics of All-on-4 immediate loading implant denture in severe periodontitis. Methods. Totally, 60 patients with dentition loss caused by severe periodontitis who were admitted to our hospital from February 2017 to February 2019 were selected. The patients were randomly divided into the observation group (n = 30) and the control group (n = 30) according to different restoration methods. The control group was used in traditional implant restoration treatment, and the observation group was used in All-on-4 immediate loading implant denture restoration. The clinical effect, periodontal index, aesthetic effect, and complications of the two groups were compared, and the levels of serum leptin (LEP), tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), and interleukin-6 (IL-6) were measured. Results. The total effective rate of the observation group (83.33%) was higher than that of the control group (60.00%) (
P
<
0.05
). After treatment, the plaque index, gingival sulcus bleeding index, and depth of exploration of the two groups were lower than those before treatment (
P
<
0.05
), and there was no significant difference between the two groups (
P
>
0.05
). After treatment, the serum LEP, TNF-α, CRP, and IL-6 in both groups were lower than before treatment, and the serum LEP, TNF-α, CRP, and IL-6 in the observation group were lower than that in the control group (
P
<
0.05
). The aesthetic rate of teeth in the observation group (90.00%) was higher than that in the control group (66.67%) (
P
<
0.05
). There was no significant difference in the total incidence of complications between the two groups (
P
>
0.05
). Conclusion. All-on-4 immediate loading implant denture has a good effect in the treatment of severe periodontitis, which is conducive to maintaining periodontal health, reducing the level of inflammation, improving aesthetics, and has high safety.