With the development of deep and ultra-deep wells, there is a need to enhance the rheological and filtration properties of water-based drilling fluids under high temperature and salinity conditions. In this study, maltodextrin polymer nanospheres (MDPN) were synthesized through cross-linking maltodextrin and methylene bisacrylamide (MBA) via inverse emulsion polymerization. Then, the polymer MDPN-DAN was synthesized via aqueous solution polymerization, using maltodextrin polymer nanospheres, N, N-dimethylacrylamide (DMAA), 2-acrylamide-2-methylpropanesulfonic acid (AMPS), and N-vinylpyrrolidone (NVP) as raw materials. Structural characterization confirmed the successful synthesis of the polymer MDPM-DAN, with a median particle size of 234.4 nm. Thermogravimetric analysis revealed a thermal decomposition temperature of 242 °C for MDPM-DAN. This polymer demonstrated excellent settling stability at 220 °C in high-temperature and weakly alkaline environments. Rheological assessments demonstrated a 754 % enhancement in the drilling fluid’s rheological properties when MDPM-DAN was added compared to the base mud. MDPM-DAN demonstrated significant reduction in filtration loss, with polymer mud aged at 220 °C showing only 5.6 mL of loss, and polymer mud aged at 220 °C with 15 wt% NaCl exhibiting 8.9 mL loss. The filtration loss reduction mechanism elucidated that MDPM-DAN could adsorb onto bentonite particles via hydrogen bonds, while nanoparticles filled the micropores of the filter cake, promoting the formation of a dense filter cake. Furthermore, plugging experiments showcased MDPM-DAN’s ability to block nano-pore throats, with the molecular chain’s amide groups reinforcing the plugging through hydrogen bonding with rocks, while bentonite coats the micro-pore throats.