Purpose To compare the short-term restorative effect and periodontal health status of restorations with different materials in full-crown restoration of mandibular premolar tooth defects. Methods A total of 105 cases (123 affected teeth) of mandibular premolar tooth defects who visited the Department of Stomatology between January 2019 and January 2020 were selected, of which 58 cases (68 affected teeth) restored with cobalt-chromium alloy porcelain crowns were included in the metal-ceramic crown (MCC) group and 47 cases (55 affected teeth) repaired by zirconium dioxide all-ceramic crowns were assigned to the zirconia crown (ZC) group. The restorative effect, inflammatory factors (high-sensitivity C-reactive protein (hs-CRP) and tumor necrosis factor-α (TNF-α)) and periodontal health indicators (human cartilage glycoprotein-39 (YKL-40), resistin, aspartate aminotransferase (AST), and alkaline phosphatase (ALP)) after treatment, and the occurrence of adverse reactions were compared between the two groups. Results The ZC group outperformed the MCC group in terms of margin fitness, restoration fracture, gingival condition, and color matching. After restoration, hs-CRP and TNF-α were statistically decreased in both groups, while YKL-40, resistin, AST, and ALP were significantly increased; and compared with the MCC group, hs-CRP, TNF-α, YKL-40, resistin, AST, and ALP were lower in the ZC group. The ZC group also scored statistically higher in retention effect, aesthetic effect, masticatory function, voice function, and comfort. Moreover, the ZC group had a higher total effective rate and a lower incidence of adverse reactions than the MCC group, with statistical significance. Conclusions Zirconia dioxide all-ceramic crowns contribute to a better short-term restorative effect in the full-crown restoration of mandibular premolar tooth defects, with little impact on periodontal health and high patient satisfaction, which deserves popularization and application.