Purpose: Ischemia and reperfusion (I/R) can cause significant functional impairments in cells and tissues depending on the duration of ischemia. To date, many alternative treatments have been utilized to address this damage. We aimed to research the protective efficacy of taxifolin (Tax), a natural antioxidant, against liver I/R injury in terms of biochemical, histopathologic, and immunohistochemical parameters. Methods: The rats utilized in our study were randomly chosen and divided into four equal groups. Group 1 (n = 7), sham group received 1 mL saline orally; group 2 (n = 7), Tax group; Group 3 (n = 7), I/R group; group 4 (n = 7), Tax + I/R group as designated. The entire study was performed under general anesthesia with protection of animal welfare. Malondialdehyde (MDA) and interleukin-6 (IL-6) were analyzed from blood samples. Proapoptotic (B-cell lymphoma 2 [Bcl-2]-associated X protein [Bax]) and antiapoptotic (Bcl-2) amendments in cells were reviewed. Results: MDA grades were lower in the Tax+I/R group compared to the I/R group. Likewise, IL-6 grades were lower in the Tax + I/R group, histologic examinations showed that Bax proteins were less expressed in the Tax + IR group, and Bcl-2 proteins were intensely expressed in the Tax group. Conclusion Taxifolin applied before liver I/R demonstrated favorable effects on inflammation, oxidative stress, and proapoptotic changes.