To overcome the negative effects of high temperature and salt pollution on the performance of drilling fluid in deep and ultra-deep wells, it is imperative to develop a high- temperature-and salt-resistant filtrate reducer. A zwitterionic quaternary copolymer (DADN) of N, N-dimethylacrylamide (DMAA), 2-acrylamido-2-methylpropane sulfonic acid (AMPS), diallyl dimethyl ammonium chloride (DMDAAC), and N-vinylcaprolactam (NVCL) was synthesized in an aqueous solution by free radical copolymerization reaction. The composition, structure, and thermal stability of the copolymers were characterized by Fourier transform infrared spectroscopy (FT-IR), proton nuclear magnetic resonance (1H NMR), Gel Permeation Chromatography (GPC), elemental analysis and thermogravimetric analysis (TGA), respectively. Furthermore, the filtration loss reduction performance of DADN was evaluated according to the American Petroleum Institute (API) standard. The mechanisms of filtrate loss reduction and salt resistance were revealed based on the transmission electron microscopy (TEM) analysis, adsorption isotherm and zeta potential analysis for the water-based drilling fluid (WBDF) containing DADN, and the scanning electron microscopy (SEM) analysis, energy-dispersive spectrometry (EDS) analysis and Brunner–Emmet–Teller (BET) analysis for the corresponding filter cake. The results showed that the thermal decomposition of DADN mainly happened over 298 ℃. Meanwhile, DADN exhibited the most outstanding filtration loss reduction ability compared to three commercially filtrate reducers (Driscal D, CMC and PAC-Lv). Specifically, the filtration losses of Driscal D/WBDF, CMC/WBDF and PAC-Lv/WBDF were 18.2, 31.2 and 24.8 mL after hot rolling at 220 °C for 16 h, respectively, while the filtration loss of DADN was only 6.5 mL. It was found that 2% DADN showed excellent filtration loss reduction ability at 220 °C and 15% NaCl. As confirmed by the SEM, EDS and adsorption isotherm results, strong adsorption of DADN on bentonite was obtained even under a high temperature and high-salinity environment. In particular, in the high-salinity environment, a firm “star network” structure formed by bentonite/DADN was observed by TEM, significantly improving the colloidal stability and filter cake compactness of WBDF.