Dynamic balance disorders are common impairments in People with Multiple Sclerosis (PwMS) leading to gait disorders and a higher risk of falling. However, the assessment of dynamic balance is still challenging and instrumented indexes provide objective and quantitative data of CoM movement and Base of Support, which are considered that are two key factors describing dynamic balance. This study aims at validating recent instrumented indexes based on the inverted pendulum model and characterizing dynamic balance disorders in PwMS. We clinically assessed 20 PwMS and we collected instrumented gait data through an optoelectronic system. Data from 20 Healthy Subjects (HS) were also considered as normative reference. Margin of Stability by HoF (MoS_Hof) and by Terry (MoS_Terry) at midstance, and Foot Placement Estimator (DFPE) at heel strike were calculated in mediolateral (ML) and anteroposterior (AP) directions, for both less affected and most affected sides for PwMS and for dominant and non-dominant side for HS. MoS_HOF well discriminated between PwMS and HS, followed by MoS_TERRY in ML direction (Mos_HOF: PwMS = 130.0 ± 27.2 mm, HS = 106.5 ± 18.6 mm, p < 0.001, MoS_TERRY: PwMS = 75.1 ± 24.3 mm, HS = 56.5 ± 23.4 mm, p < 0.02). MoS_HOF and MoS_TERRY discriminated between sides in both directions in PwMS. DFPE did not discriminate between groups and sides. Moderate correlations were found between all three indexes and clinical balance scales (from r = 0.02 to r = 0.66), energy recovery (from r = -0.77 to r = -0.11), single stance time (from r = -0.11 to r = 0.80) and step length (from r = -0.83 to r = -0.20). MoS_HOF resulted in the best index to describe dynamic balance disorders in PwMS: they keep CoM position far from the lateral and as close as possible to the anterior boundary of the Base of Support as preventive strategies to control balance perturbations. Furthermore, PwMS seem to use different preventive strategies in accordance with the specific lower limb impairments. This alters the physiological gait mechanisms increasing the energy expenditure and decreasing gait quality and dynamic balance.