Prostatitis is an inflammatory condition that is related to multiple infectious agents, including bacteria and fungi. Traditional herbal extracts proved efficacious in controlling clinical symtpoms associated with prostatitis. In this context, the aim of the present study was to explore the efficacy of water extracts from S. virga-aurea, O. spinosa, P. boldus, E. angustifolium and P. niruri against bacterial (Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Bacillus cereus) and fungi strains (Candida albicans; C. tropicalis), involved in prostatitis. Additionally, anti-mycotic activities were tested against multiple species of dermatophytes (Tricholosporum rubrum, T. tonsurans, T. erinacei, Aspergillus crocatum, A. quadrifidum, A. gypseum, A. currey, A. insingulare), as well. Antioxidant effects were also evaluated in isolated rat prostate challenged with lipopolysaccharide (LPS), whereas phytochemical analyses were conducted to identify and quantify selected phenolic compounds, in the extracts. Finally, a bioinformatic analysis was conducted to predict putative human and microbial enzymes targeted by extracts’ phytocompounds and underlying the observed bio-pharmacological effects. The phytochemical analysis highlighted that rutin level could be crucial for explaining the highest antibacterial activity of P. boldus extract, especially against E. coli and B. cereus. On the other hand, in the E. angustifolium extract, catechin concentration could partially explain the highest efficacy of this extract in reducing lipid peroxidation, in isolated rat prostate stimulated with LPS. Concluding, the results of the present study showed antimicrobial and protective effects induced by water extracts of S. virga-aurea, P. boldus, E. angustifolium, P. niruri and O. spinosa, that are related, at least partially to phenolic composition of the phytocomplex. Additionally, the observed differences in extract efficacy supports the association of the aforementioned extracts, in order to improve the pharmacological spectrum. This could be in crucial for counteracting the burden of oxidative stress and inflammation occurring in bacterial prostatitis.