The rapid development of anthelminthic resistance has limited the success of traditional control programmes in several countries, thereby forcing the researchers to search for alternatives. In vitro anthelmintic activities of crude aqueous and hydro-alcoholic extracts of the leaves of Eucalyptus globulus were investigated against the egg and larvae of naturally infected sheep. In the phytochemical analyses, tannins and flavonoids were the main metabolites identified in the extract. The aqueous extract of E. globulus was also investigated for in vivo anthelmintic activity in naturally infected sheep. The various blood parameters, coupled with effects on marker enzymes and antioxidant status, were evaluated during the trial period. Methanolic extract showed better ED50 (3.756 mg/ml) and ED99 (33.809 mg/ml) values in comparison with aqueous extract (ED50 = 1.502 and ED99 = 7.10 mg/ml) in the egg hatch assay. Inverse was true in larval development and larval paralysis tests. The aqueous extract's ED50 = 19.994 and ED99 = 108.931 mg/ml values in the larval development test and ED50 = 19.994 and ED99 = 108.931 mg/ml in the larval paralysis test were more potent than those of its methanolic counterpart with ED50 = 15.595 and ED99 = 94.493 mg/ml and ED50 = 15.595 and ED99 = 94.493 mg/ml, respectively. A significant amount of 66% faecal egg count reduction was observed in in vivo trail using the aqueous extract on day 21 post treatment, although in initial stages it showed 58.0 and 80% effectiveness on days 7 and 14 post treatment. Though the FCER reduction was somewhat lower in terms of comparison with albendazole, nevertheless, significant and prolong reduction was noticed. No deleterious ill effect was found in any of the haematological and biochemical parameters suggesting that the plant could be safer for use in sheep. Though significant changes were observed in SGPT, RBCs, Hb and RDWc levels, other parameters showed nonsignificant variations within the normal range in the stipulated time of of herbal trial period. Based on the results of the present study, it could be very well concluded that leaves of E. globulus possess good level of anthelminthic efficacy; further research is thereby warranted before recommending it for use in nematode control programme in ovines.