A new type of adsorbent with efficient antibacterial activity (PAM-AO-PHGC) for uranium extraction from seawater was prepared by crosslinking of polyhexamethylene guanidine hydrochloride (PHGC) and amidoxime group (AO) under the condition of glutaraldehyde. The functional groups and morphology of the material were characterized by Fourier transform infrared spectroscopy (FT-IR) and scanning electron microscopy (SEM). The uranium adsorption performance of PAM-AO-PHGC under different adsorption conditions (pH, salt ionic concentration and adsorption time) was studied by adsorption experiments. The equilibrium adsorption capacity of PAM-AO-PHGC in simulated seawater reaches 231.0 mg/g, and the adsorption process conforms to the pseudo-second-order kinetic equation. Under the conditions of seawater pH (8.0) and high salt ion concentration (0.5 mol/L NaCl), the adsorbent exhibits excellent uranium adsorption efficiency. In addition, PAM-AO-PHGC can effectively inhibit the growth of E. coli, S. aureus, and two types of vibrios which are ubiquitous in the ocean. The introduction of polyguanidine has great potential to solve the biofouling problem in the process of uranium extraction from seawater.