The honeybees (Apis mellifera) population is declining. The involved causes may be pathogens (mites, viruses and bacteria) and parasites, due to honeybee's compromised immune system, leading to various bee-associated infections. Therefore, the present study assessed the comparative efficacy of plant extracts, including neem (Azadirachta indica) and Barbaka (Vitex trifolia) against gut bacteria and ectoparasitic mite Varroa destructor of honeybee A. mellifera (Hymenoptera: Apidae). The in vitro activities of the plant extracts were determined by using standard methods against five bee gut bacterial isolates, including the well-known bee pathogenic bacteria Paenibacillus larvae. Miticides were also assessed in field against honeybee mites. The obtained results from the phytochemical screening of Barbaka and neem extracts efficiency showed inhibitory zones with diameters of 23 mm with 60 mg/mL against P. larvae and 14 mm with 60 mg/mL against Escherichia coli, respectively. None of the extracts proved to be effective against Salmonella enterica and the neem extract showed intermediate activity against Bacillus subtilis and Staphylococcus hominis. Likewise, Barbaka plant extracts were not effective against B. subtilis. Similarly, the relative treatment efficacies of neem and Barbaka extracts, together with conventional miticides against honeybee Varroa mites, varied significantly. However, the effect of Barbaka and neem extracts on the mite-infested colonies was lower than the effect of other treatments, but it was also higher than in the control colonies. This study concluded that Barbaka and neem extracts have antibacterial and miticidal activity and are reasonably safe. However, more trials have to be conducted, in order to validate these results.