The introduction of resistant and lightweight materials in the construction industry has led to civil structures being vulnerable to excessive vibrations, particularly in footbridges exposed to human-induced gait loads. This interaction, known as Human–Structure Interaction (HSI), involves a complex interplay between structural vibrations and gait loads. Despite extensive research on HSI, the simultaneous effects of lateral structural vibrations with fundamental frequencies close to human gait frequency (around 1.0 Hz) and wide amplitudes (over 30.0 mm) remain inadequately understood, posing a contemporary structural challenge highlighted by incidents in iconic bridges like the Millennium Bridge in London, Solferino Bridge in Paris, and Premier Bridge in Cali, Colombia. This paper focuses on the experimental exploration of Structure-to-Human Interaction (S2HI) effects using the Human–Structure Interaction Multi-Axial Test Framework (HSI-MTF). The framework enables the simultaneous measurement of vertical and lateral loads induced by human gait on surfaces with diverse frequency ranges and wide-amplitude lateral harmonic motions. The study involved seven test subjects, evaluating gait loads on rigid and harmonic lateral surfaces with displacements ranging from 5.0 to 50.0 mm and frequency content from 0.70 to 1.30 Hz. A low-cost vision-based motion capture system with smartphones analyzed the support (Tsu) and swing (Tsw) periods of human gait. Results indicated substantial differences in Tsu and Tsw on lateral harmonic protocols, reaching up to 96.53% and 58.15%, respectively, compared to rigid surfaces. Normalized lateral loads (LL) relative to the subject’s weight (W0) exhibited a linear growth proportional to lateral excitation frequency, with increased proportionality constants linked to higher vibration amplitudes. Linear regressions yielded an average R2 of 0.815. Regarding normalized vertical load (LV) with respect to W0, a consistent behavior was observed for amplitudes up to 30.0 mm, beyond which a linear increase, directly proportional to frequency, resulted in a 28.3% increment compared to rigid surfaces. Correlation analyses using Pearson linear coefficients determined relationships between structural surface vibration and pedestrian lateral motion, providing valuable insights into Structure-to-Human Interaction dynamics.