Herein, we report the synthesis of an alternating copolymer (ACP) with a bio-reducible amphiphilic polydisulfide backbone and highlight the impact of the alternating monomer connectivity on the self-assembly, morphology, chain-exchange dynamics, drug-release kinetics, and enzyme activity inhibition. Condensation polymerization between hydrophobic 1,10-bis(pyridin-2-yldisulfaneyl)decane and hydrophilic 2,3-mercaptosuccinic acid (1.04 : 1.00 ratio) generated amphiphilic ACP P1 ( M w = 8450 g mol -1 , Đ = 1.3), which exhibited self-assembly in water, leading to the formation of an ultra-thin (height <5.0 nm) entangled fibrillar network. In contrast, structurally similar amphiphilic random copolymer P2 exhibited a truncated irregular disc-like morphology under the same conditions. It is postulated that due to the perfect alternating sequence of the hydrophobic and hydrophilic segments in P1, its immiscibility-driven aggregation in water leads to a pleated structure, which further assembles and forms the observed long fibrillar structures, similar to crystallization-driven self-assembly. In fact, wide-angle X-ray diffraction (WXRD) analysis of a lyophilized P1 sample showed sharp peaks, indicating its crystalline nature (approximately 37% crystallinity), and these were completely missing for P2. The effect of such distinct self-assembly on the chain-exchange dynamics was probed by fluorescence resonance energy transfer (FRET) using 3,3'-dioctadecyloxacarbocyanine perchlorate (DiO) and 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI) as the FRET-donor and -acceptor, respectively. For DiI- and DiO-entrapped solutions of P1, when mixed, no prominent FRET appeared even after 24 h. In sharp contrast, for P2, intense FRET emission occurred, and the FRET ratio (approximately 0.9) reached saturation in approximately 15 h, indicating the greatly enhanced kinetic stability of P1 aggregates. Glutathione-induced release of encapsulated Nile red showed much slower kinetics for P1 compared to that of P2, which was corroborated by the observed slow chain-exchange dynamics of the highly stable alternating copolymer assembly. Furthermore, the well-ordered assembly of P1 exhibited an excellent surface-functional group display (zeta potential of -32 mV compared to -14 mV for P2), which resulted in the effective recognition of the α-chymotrypsin (Cht) protein surface by electrostatic interaction. Consequently, P1 significantly (>70%) suppressed the enzymatic activity of Cht, while in the presence of P2, the enzyme was still active with >70% efficacy.