This study characterized two novel bacteriophage-derived endolysins, LysPEF1-1 and LysPEF1-2, and evaluated their antibacterial and antibiofilm activities against multidrug-resistant Enterococcus faecalis. LysPEF1-1 exhibited a broader lytic spectrum and stronger antibacterial activity than LysPEF1-2, while both endolysins remained active under a wide range of environmental conditions. Their combined application produced a synergistic effect, significantly reducing planktonic bacterial cells, inhibiting biofilm formation, and enhancing biofilm removal compared with individual treatments. These findings demonstrate that the combined use of LysPEF1-1 and LysPEF1-2 represents a promising alternative antimicrobial strategy for controlling multidrug-resistant E. faecalis infections.