Arsenic is a major environmental toxicant as well as a human carcinogen which is present in large amounts in the environment. Biotransformation of arsenic generates reactive methylated species which can bind and facilitate chromosomal and DNA damage. This work investigated the effects of chrysin on sodium arsenic-induced damage on lipid, protein and chromosome of male Wistar rats.Rats were divided into six groupsand treated daily as follows normal control; 1a and 1b, 10mg/kg sodium arsenite as negative control, 10mg/kg chrysin as positive control, co-administration of sodium arsenite and chrysin, chrysin followed by sodium arsenite and sodium arsenite followed by chrysin. At the end of the experiment, the animals were sacrificed and lipid peroxidation, protein carbonyl and DNA fragmentation in liver, blood, brain and bone marrow cells micronuclei were assayed for. In silico molecular docking of S-adenosyl-methionine-dependent methyltransferase in the presence of chrysin was conducted. Chrysin significantly (p<0.05) decreased the level of lipid peroxidation, protein carbonyls and DNA fragmentation in blood, liver and brain tissues compare to group treated with sodium arsenite only. Chrysin significantly (p<0.05) reduced the level of micronuclei generated in bone marrow cells. Furthermore, chrysin was able to dock into the active site of SAM-dependent methyltransferase with strong hydrogen bond and hydrophobic interactions.The binding energy of the docking was -99.82kJ/moland predicted inhibition constant (Ki) of 0.959µM.Chrysin at 10mg/kg bodyweight was shown to exhibits ameliorative, preventive and curative in effects. This study might have unraveled the beneficial effects of chrysin against sodium arsenite-induced chromosomal and DNA damage, which could be due to inhibition of SAM-dependent methyltransferase.