Background: Arsenic (As) is a naturally occurring semimetallic element that is classified as a toxicant and a human carcinogen. Diallyl trisulphide (DATS), an organosulphur compound, is an antioxidative substance that is extracted from garlic ( Allium sativum ). Erythrocytes are very expedient models to understand the susceptibility of membrane to oxidative damage induced by different xenobiotic compounds. Arsenic has been reported to induce oxidative stress to erythrocytes due to lipid peroxidation and alteration in defence mechanism as erythrocytes are the first target that arsenic compounds attack in the body after systemic absorption. In the light of this fact, the purpose of this study is to characterise the ameliorative effect of DATS on arsenic-induced oxidative stress in rat erythrocytes. Methods: Experimental rats were randomly divided into four groups and treated orally for 28 days: control, As [5 mg/kg body weight (BW)] treated, As+DATS (80 mg/kg BW) treated, DATS (80 mg/kg BW) treated and As+vitamin C (100 mg/kg BW) treated. Oxidative stress in erythrocytes was recorded by estimating plasma marker enzymes, plasma and erythrocyte membrane oxidative stress markers, erythrocyte membrane antioxidant enzymes and non-antioxidant enzymes, etc. Results: Oral administration of arsenic at 5 mg/kg BW per day elevated the levels of plasma marker enzymes, namely, aspartate transaminase (AST), alanine transaminase (ALT), acid phosphatase (ACP), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), and γ-glutamyl transferase (γGT) (U/L) with significantly increased lipid peroxidation markers such as thiobarbituric acid reactive substances (TBARS), malondialdehyde (MDA), lipid hydroperoxides (LH), conjugated dienes (CD), and protein carbonyl (PC) contents were also elevated in As-treated rat plasma and erythrocytes. The levels of non-enzymatic antioxidants (reduced glutathione, vitamins C and E) and enzymatic antioxidants such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione S -transferase (GST), glutathione reductase (GR), and glucose-6-phosphate dehydrogenase (G6PD) were also decreased in As-treated rats. The toxic effect of As significantly decreased the activities of membrane-bound ATPases (Na +/ K + -ATPase, Mg 2+ -ATPase, and Ca 2+ -ATPase), with a significant increase in% tail DNA of rat lymphocytes measured by means of a single-cell gel electrophoresis assay. Administration of DATS for 28 days significantly reduced the levels of plasma markers. The levels of TBARS, MDA, LH, CD, and PC were significantly decreased and there was a significant increase in ATPase activities and non-enzymatic and enzymatic antioxidants on treatment with DATS in a dose-related manner. Conclusions: All these changes were supported by reduction of DNA damage in lymphocytes with DATS treatment. DATS at a dose of 80 mg/kg BW was found to be most effective and the results revealed the same. The results of the study showed that DATS shows a protective effect against As-induced oxidative stress in rat erythrocytes and lymphocytes.