The study was conducted to determine the phenolic contents, in-vitro antioxidant activity and in-vivo anti-plasmodial activity of methanolic leaf extract of Azadirachta indica (Dongoyaro) and its effect on some biochemical parameters in Swiss albino mice infected with Plasmodium berghei NK 65. Swiss albino mice were inoculated intraperitoneally with Plasmodium berghei NK65. The mice were grouped into six groups, five per group. Group I were not infected with P.berghei, Group II and III served as both the negative and positive control while Group IV, V, and VI were treated with 200, 400, and 800 mg/kg body weight of methanolic leaf extract of A. indica. The qualitative phytochemicals in the extract include tannin, anthraquinone, flavonoids, phlobatanin, saponin etc. The amount of total phenol, flavonoids, alkaloids and total proanthocyanidins present in the extract are 148.22 mg PE / g DW, 1.5%, 5.3% and 0.67±0.2 mg quercetin/g of dry plant material respectively. In the in-vitro antioxidant assay, A. indica was found to have FRAP, DPPH and H2O2 scavenging activity. The median lethal dose LD50 was estimated to be >5000mg/Kg body weight. The extract caused 47.80%, 50.96% and 52.30% suppression in parasitaemia at 200, 400 and 800mg/kg body weight respectively while Chloroquine exerted 100% suppression at 5mg/kg body weight. The curative test shows that the different concentration of the extract exert a growth inhibition of 50.1%, 74.57% and 73.68% at 200, 400, 800mg/kg body weight respectively while Chloroquine cleared the parasites by 94.07% at 5mg/kg body weight. The Hematological parameters showed that the extract is not hematotoxic since it significantly (P<0.05) reduced WBC count, and increase RBC, HGB, and HCT values in the treated mice compared to the infected untreated mice. The liver biomarker enzymes show that there was a significant increase (P>0.05) in plasma AST, ALT, ALP and GGT in the untreated infected group compared to other groups, this signify hepatic damage in group II animals. This may also signifies hepatoprotective effect of the extract on the Swiss mice infected with P. berghei. The infected untreated and the infected treated animals all have higher plasma creatinine and urea values compared to normal healthy animals. There was a significant decrease (P<0.05) in total plasma protein in group II mice compared to the mice in other groups.