The majority of physiologic activities in the brain and associated illnesses include multiple neurotransmitter systems and their dysfunctional consequences, which entails elucidation of the interaction among distinct pathways. In light of recent revaluations in schizophrenia research, this review focuses on the interplay between dysregulations of neurotransmitter systems, including the effects of systemic neuroinflammation and a disruption of Wnt-pathways. This includes a detailed network-circuit illustration centered on dysregulated glutamatergic transmission and NMDA receptor hypofunction explaining the role of dopamine and glutamate, their receptors like D2R, NMDAR, AMPAR, and their agonist/co-agonist, antagonist, along with a synergism of downstream effector molecules like Akt/GSK-3, Wnt/β-catenin, Cytokines, CRP, NF-κB, while simultaneously illuminating involvement of inflammatory, oxidative, and Kyunurenic mechanisms, and their implications towards the progression of schizophrenia. We are for the first time producing a comprehensive list of associated biomarkers with their key roles and features. Schizophrenia is becoming more prevalent in African countries, and existing antipsychotic therapeutic regime provides little assistance, other from being inaccessible, ineffective, and laden with complications. It is critical to focus on traditional knowledge; thus, in the second section, we present a detailed list of 27 African plant species across 23 families, replete with phytocomponents proven effective in in-vivo models and their likely mechanism of action. In essence, the first section of the review presents the underlying mechanism of schizophrenia development via an interactive signaling pathways approach and a list of identified biomarker components, while the second section presents a comprehensive list of African ethnomedicinal plants used in disease management.