Efficient ionization is a necessary condition for mass spectrometric analysis, but many compounds fail to ionize well enough to yield sufficient detection limits. Triboelectric nanogenerators (TENG) coupled to nanoelectrospray ionization (nanoESl) mass spectrometry (MS) are a highly effective approach to high sensitivity MS analysis. Here, we report on new, large-area TENG that constructively leverage the relationship between electrode size, created charges, and open-circuit voltage, leading to wider chemical coverage. Large-area TENG were found to also promote electrospray gas-phase oxidation reactions that enabled double bond position pinpointing for unsaturated lipids and species-specific lipid quantitation. Furthermore, large-area TENG MS of proteins was observed to yield higher charge state distributions (i.e., supercharging) without the need for high surface tension additives.