Nowadays, the bacterial resistant infection risks to antibiotics have the limelight of developing new and natural antibacterial biomaterials. So, this work aimed to prepare drug carriers for Ceftriaxone (CFX) loading based on hydrogel nanocomposites for increasing the CFX loading capacity and improving the antibacterial properties of the hydrogels. Hence, a novel nanocomposites based on Ca-alginate hydrogels were prepared as antibacterial model. The morphology, textural, and the molecular interaction between the Mesoporous silica nanoparticles (MSNs) and the hydrogels were evaluated by using SEM, DCS, and FT-IR characterization techniques and loading efficiency was calculated. The loading efficiencies of (0, 5, 10 % MSNs) loaded with CFX were 2.379, 19.597 and 16.05 %, respectively. Furthermore, the antibacterial property of the hydrogels was tested by using colony forming test at three different loaded CFX concentrations. The results showed that, as MSNs % was increased in the alginate matrix, the loading CFX concentration increased. Thus, at 10% MSNs of 425.6 µg/ml CFX showed a significant viability % with (p** < 0.01) that was reached to 15.473% ± 0.399 relative to negative control. So, the hydrogels were to be used as a good CFX drug carrier and demonstrated a bactericidal effect against gram positive and gram negative bacteria.