Deltamethrine (DLM) is a synthetic pyrethroid with broad spectrum activities against acaricides and insects. Widely used for agricultural and veterinary purposes, its human and animal exposure occurs by ingestion of contaminated water and food and leads to serious health problems. Kefir is fermented milk with numerous health favors counting restorative properties of bacterial flora, immune system stimulation, cholesterol reduction, as well as anti-mutagenic and anti-tumor properties. The present study was undertaken to examine the hepatoprotective and antioxidant potential of kefir against DLM toxicity in male Wistar albino rats. DLM-treated animals revealed a significant increase in serum biochemical parameters as well as hepatic protein and lipid oxidations but caused an inhibition in antioxidant enzymes. Additionally, we have observed an increase in hepatocyte DNA damages. This toxic effect was confirmed by histological study. Kefir administration normalized the elevated serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (T bilirubin), and cholesterol. It also reduced DLM-induced protein carbonyl (PC) and malondialdehyde (MDA) formations. Furthermore, Kefir treatment restored catalase (CAT) and superoxide dismutase (SOD) activities. The co-treatment as well as the pre-treatment by kefir showed an improvement of oxidative status as well as suppressed inflammation and DNA damages. However, the pre-treatment seems to be the most efficient. Therefore, it could be concluded that kefir is a natural product able to protect against the hepatotoxic effects of DLM by its free radical-scavenging and potent antioxidant activity.