The present study aimed to investigate the effects of periodontitis on kidneys and the protective role of crocin in periodontitis-induced kidney damage. Ethics committee approval was obtained and 30 Wistar rats were randomly divided into 3 groups of 10 rats: Control (C), Periodontitis (P), and Periodontitis + Crocin (P + Cr). After the treatments, rat kidney tissues were incised under anesthesia and blood samples were collected. Biochemical and histopathological analyses were conducted on the samples. Malondialdehyde (MDA), total oxidant status (TOS), and oxidative stress index (OSI) increased in P group rat kidney tissues; urea, creatinine, Tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin 1β (IL-1β) levels increased in the serum; glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) and total antioxidant status (TAS) levels were reduced in rat kidney tissues, and renal histopathology deteriorated. In the P + Cr group, we observed improvements in biochemical and histopathological parameters when compared with the P group. Periodontitis (P) led to deterioration in oxidative stress parameters and histopathology by increasing the oxidants in kidney tissue. P also led to inflammation in the blood of the rats. Periodontitis + Crocin (P + Cr) administration alleviated the effects of P due to powerful antioxidant anti-inflammatory properties. Cr could be employed as a protective agent in P-induced inflammation and oxidative damage.