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A new insight into the synthesis of the herbal plant (<i>White poplar</i>, <i>Poplus alba</i>) leave extract using chitosan nanocapsule was studied. The in vitro antibacterial activity of chitosan white poplar nanocapsule (CWPNC) against <i>Streptococcus agalactiae</i> (<i>S. agalactiae</i>) was determined. About 120 fish were categorized for 7 days into four groups. The first and second (CWPNC) groups were treated with 0 mg/L and 3 mg/L CWPNC in the water, respectively, without being challenged; the first group was a control. The third (<i>S. agalactiae</i>) and fourth (CWPNC + <i>S. agalactiae</i>) groups were treated with 0 and 3 mg/L CWPNC, respectively, and challenged with <i>S. agalactiae</i> (0.5 × 10⁷ CFU/mL). The obtained results revealed that CWPNC had an in vitro antibacterial activity against <i>S. agalactiae</i>. Moreover, <i>S. agalactiae</i> infection caused a significant elevation (<i>p</i> < 0.05) in the lipid peroxidation (malondialdehyde) and hepatorenal biomarkers, as well as the lowest significant (<i>p</i> < 0.05) survival rate (33.33%). Moreover, a significant depletion (<i>p</i> < 0.05) in the level of antioxidants (catalase and superoxide dismutase) and the immune indicators (immunoglobulin, lysozyme activity, and complement 3) were the consequences of <i>S. agalactiae</i> infection. Treatment of the infected fish with 3 mg/L CWPNC alleviated these bad circumstances.