Breast cancer is the most common cancer in women worldwide, and the incidence and mortality rates have been increasing. Chemotherapy remains the main treatment strategy for triple-negative breast cancer (TNBC). However, multidrug resistance often affects the efficiency of chemotherapy and is the main reason for the failure of current clinical cancer treatments in patients with TNBC. Therefore, we developed a nanocarrier with biodegradable polymer materials and encapsulated a clinical chemotherapeutic drug to form an active targeting nanoparticle drug delivery system. In this study, the biopolymers fucoidan (FD) and arginine-gelatin (Arg-GL) were used to synthesize nanoparticles through electrostatic forces and to encapsulate the chemotherapeutic drug doxorubicin (Dox). Our study demonstrated that the Dox-loaded FD/Arg-GL nanoparticles exhibited high drug loading capacity and pH-responsive characteristics. The results of in vitro experiments showed that the nanoparticles actively targeted P-selectin expressed by cancer cells, thereby enhancing the anticancer effect and inhibiting the migration and invasion of Dox-resistant TNBC cells. Moreover, in vivo studies further confirmed the antitumor activity of the nanoparticles, as they enabled the drug to accumulate at the tumor site. In conclusion, Dox-loaded FD/Arg-GL nanoparticles offer a potential therapeutic strategy for drug-resistant TNBC.