This study aimed to evaluate the in vitro antiviral activity of ethanolic extracts from Azadirachta indica and Melia azedarach during the replication cycle of the CAEV-Cork and MVV-K1514 strains, both part of the small ruminant lentivirus (SRLV) group, in ovine third eyelid (OTE) cells. The crude extracts (CE), along with the ethyl acetate (EAF) and methanol (MF) organic fractions from these plants, were tested in treatments applied before, during, and after viral inoculation of the CAEV-Cork and MVV-K1514 strains in separate OTE cell cultures. Following these treatments, the most effective results were subjected to viral titration analysis. The findings indicate that the EAF of A. indica and M. azedarach may have reduced the viral titer of the CAEV-Cork strain by 316-fold after inoculation and by 1.995-fold when applied concomitantly with inoculation, respectively. For the MVV-K1514 strain, the EAF of A. indica achieved a 1,000-fold inhibition when applied simultaneously with viral inoculation. These results suggest that extracts from Meliaceae plants influenced all phases of the SRLV replication cycle, significantly inhibiting the activity of both viral strains, although complete viral elimination was not achieved.