Gait analysis is often used to study locomotor alterations in people with multiple sclerosis (PwMS), but the large number of extracted variables challenges the interpretability. In this paper, we analysed gait alterations by combining the Gait Profile Score (GPS), which summarizes kinematic locomotor deviations, and Statistical Parametric Mapping (SPM), which compares kinematics and kinetics over the whole gait cycle. Eleven PwMS and 11 speed-matched Healthy Controls (HC) underwent overground gait analysis. GPS were compared through independent-samples t-tests; sagittal-plane kinematics and power at hip, knee, and ankle were compared through SPM Hotelling’s-T2 and SPM t-tests. Spearman’s correlation coefficients (r) between GPS and clinical outcomes were also calculated. PwMS had higher GPS than HC (PwMS = 8.74 ± 2.13°; HC = 5.01 ± 1.41°;p< 0.001). Multivariate SPM found statistically significant differences at 0–49%, 70–80%, and 93–99% of stride (p< 0.05) and univariate analysis showed reduced ankle dorsiflexion, and lower knee flexion during pre-swing and swing. GPS correlated with Expanded Disability Status Scale (r = 0.65; 95%C.I.[0.04,0.91];p= 0.04) and 2-Minute Walking Test (r = -0.65; 95%C.I.[-0.91,-0.04];p= 0.04). GPS in conjunction with SPM revealed multi-joint kinematic alterations on sagittal plane involving distal joint angles, ankle and knee, during the stance phase with no changes at the proximal level. Gait deviations were more pronounced in PwMS with higher disability and walking limitations.