Zinc oxide nanoparticles have many advantages for nano-biotechnologists due to their intense biomedical applications. ZnO-NPs are used as antibacterial agents, which influence bacterial cells through the rupture of the cell membrane and the generation of reactive free radicals. Alginate is a polysaccharide of natural origin due to its excellent properties that are used in various biomedical applications. Brown algae are good sources of alginate and are used as a reducing agent in the synthesis of nanoparticles. This study aims to synthesize ZnO-NPs by using brown algaFucus vesiculosus(Fu/ZnO-NPs) and also to extract alginate from the same alga, which is used in coating the ZnO-NPs (Fu/ZnO-Alg-NCMs). The characterizations of Fu/ZnO-NPs and Fu/ZnO-Alg-NCMs were determined by FTIR, TEM, XRD, and zeta potential. The antibacterial activities were applied against multidrug resistance bacteria of both gram-positive and negative. The results obtained in FT-TR showed there are some shifts in the peak positions of Fu/ZnO-NPs and Fu/ZnO-Alg-NCMs. The peak at 1655 cm−1, which assigned amide I-III, is present in both Fu/ZnO-NPs and Fu-Alg-ZnO-NCMs; this band is responsible for bio-reductions and stabilization of both nanoparticles. The TEM images proved the Fu/ZnO-NPs have rod shapes with sizes ranging from 12.68 to 17.66 and are aggregated, but Fu/ZnO/Alg-NCMs are spherical in shape with sizes ranging from 12.13 to 19.77. XRD-cleared Fu/ZnO-NPs have nine sharp peaks that are considered good crystalline, but Fu/ZnO-Alg-NCMs have four broad and sharp peaks that are considered semi-crystalline. Both Fu/ZnO-NPs and Fu/ZnO-Alg-NCMs have negative charges (−1.74 and −3.56, respectively). Fu/ZnO-NPs have more antibacterial activities than Fu/ZnO/Alg-NCMs in all tested multidrug-resistant bacterial strains. Fu/ZnO/Alg-NCMs had no effect onAcinetobacterKY856930,Staphylococcus epidermidis, andEnterobacter aerogenes, whereas there was an apparent effect of ZnO-NPs against the same strains.