Abnormal aggregation of α-synuclein (αS) into amyloid fibrils is a hallmark of neurodegenerative diseases such as Parkinson’s disease. In contrast, its homolog β-synuclein (βS), co-localized at presynaptic terminals, resists amyloid formation and can even inhibit αS fibrillization. However, how sequence variations affect their structural dynamics remains poorly understood. To address this, we conducted 100 independent 1000-ns atomistic discrete molecular dynamics simulations for both αS and βS monomers. Our results revealed that both proteins predominantly adopted intrinsically disordered conformations, punctuated by transient helices and β-sheets. Both αS and βS exhibited a conserved helical tendency in the first half of the N-terminal domain, while the latter half showed dynamic β-sheet characteristics, with αS displaying greater abundance. Notably, the non-amyloid component (NAC) region in αS—critical for its aggregation—frequently adopted dynamic β-sheet structures, whereas the homologous region in βS displayed a greater tendency toward dynamic helices. Despite being largely disordered, the C-terminal regions transiently interacted with β-sheet–prone segments, potentially acting as dynamic caps that limit β-sheet growth in both proteins. Free energy landscape analysis indicated a clear enthalpy–entropy trade-off: structured conformations were stabilized by lower potential energy but penalized by reduced entropy, whereas disordered states, despite higher potential energy, were entropically favored. Importantly, potential energy reduction in αS was primarily associated with β-sheet formation, while in βS it was mainly driven by helix formation. These findings offer mechanistic insight into the distinct conformational landscapes of αS and βS and establish a thermodynamic framework for understanding how sequence differences modulate their structural properties and functional roles.