A biofouling-resistant solid-contact lead ion-selective electrode (Pb2+-ISE) with enhanced stability was developed based on dendritic peptides and polyaniline-MXene composites. The biofouling-resistant dendritic peptides, characterized by their high level of hydration and relative conformational entropy, effectively inhibit nonspecific adsorption. Simultaneously, the synergy between polyaniline nanowires and MXene nanosheets is harnessed to enhance the ion-electron transfer rate, thereby improving the stability of the ISE. The fabricated Pb2+-ISEs exhibit commendable electrochemical short-term stability and can rapidly respond to potential changes within 1 second. Under bacterial solution storage conditions, the peptide-modified ISEs maintain their Nernstian response without significant alteration for up to six days. Additionally, the Pb2+-ISEs are insensitive to O2, CO2, N2, and light, making them suitable for the analysis of Pb2+ in real complex samples. The strategic design incorporating dendritic peptides as a biofouling-resistant layer and the PANI-MXene composite as a conductive layer offers an effective approach to construct low-fouling ISEs capable of operating robustly in complex systems.