A new insight into the synthesis of the herbal plant (White poplar, Poplus alba) leave extract using chitosan nanocapsule was studied. The in vitro antibacterial activity of chitosan white poplar nanocapsule (CWPNC) against Streptococcus agalactiae (S. agalactiae) 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 (S. agalactiae) and fourth (CWPNC + S. agalactiae) groups were treated with 0 and 3 mg/L CWPNC, respectively, and challenged with S. agalactiae (0.5 × 107 CFU/mL). The obtained results revealed that CWPNC had an in vitro antibacterial activity against S. agalactiae. Moreover, S. agalactiae infection caused a significant elevation (p < 0.05) in the lipid peroxidation (malondialdehyde) and hepatorenal biomarkers, as well as the lowest significant (p < 0.05) survival rate (33.33%). Moreover, a significant depletion (p < 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 S. agalactiae infection. Treatment of the infected fish with 3 mg/L CWPNC alleviated these bad circumstances.