The web-crippling failure of pultruded fiber-reinforced polymer (FRP) profiles is a challenging issue in the design of pultruded FRP structures, and this is reflected in the limited guidance provided in codes. In fact, accurate and reliable design formulae are not yet available for all loading cases, namely end-one-flange (EOF) and interior-one-flange (IOF) loading. This paper establishes web-crippling design guidelines for pultruded glass-FRP (GFRP) I-section profiles under localized one-flange loading (i.e., EOF and IOF). This work builds upon the results of experimental tests recently conducted by the authors, where all tested commercial structural profiles exhibited web-crushing failure, with none failing due to web buckling. Consequently, two separate design formulae were developed. A design formula for web-crushing failure was proposed and calibrated using experimental data. Since none of the tested profiles failed due to buckling, a new set of more slender profiles (unavailable in the market, but constrained by practical thicknesses and with rational web heights) were added to the available ones and simulated computationally. Based on these simulations, a second design formula was developed and calibrated to account for either web-crushing or combined web-buckling and web-crushing failure. As materials continue to become stronger and stiffer over time, these formulae provide a framework for anticipating the potential introduction of more slender FRP profiles in the market. Based on these results, a numerically-based direct strength method (DSM) curve was defined, featuring a unified DSM expression for EOF and IOF loading configurations.