Succinic semialdehyde dehydrogenase (SSADH) deficiency is an autosomal-recessive neurometabolic disorder caused by bi-allelic mutations in the ALDH5A1 gene. It is the most prevalent inherited disorder of GABA metabolism and is characterized by accumulation of two neuromodulators, gamma-aminobutyric acid (GABA) and gamma-hydroxybutyric acid (GHB), in the CNS. In this study, we used fourteen iPSC lines: three patient lines and sex matched parental controls and CRISPR corrected lines each transduced with hNGN2 and hDLX2-hASCL1 to generate excitatory neurons and GABAergic neurons. We show that hiPSCs can differentiate into excitatory neurons and GABAergic neurons regardless of the allelic dosage of ALDH5A1. We found that hiPSC-derived excitatory neurons display altered neurite outgrowth and synaptic development which leads to hyperactivity of the developing excitatory neuronal network. Moreover, we showed that the CRISPR correction ALDH5A1corr/corr shows similar network activity to the parental control ALDH5A1+/- suggesting that hiPSC-derived excitatory neurons network’s hyperactivation is linked to the ALDH5A1 mutation. Additionally, we identified neuron subtype-specific metabolic and gene expression changes linked to SSADH deficiency and we showed that similarly to clinical presentation, SSADHD results in increased GABA and GHB levels in hiPSC-derived GABAergic neurons. Furthermore, we developed an imaging platform based on calcium imaging and optogenetics to manipulate the network of neurons formed by hiPSC-derived GABAergic and excitatory neurons in vitro in a high-throughput fashion. Finally, we demonstrated we rescued these phenotypes using ALDH5A1 mRNA demonstrating the potential of the mRNA-based therapeutics in SSADH deficiency.