One of the main underlying mechanism of stroke, trauma and other neurodegenerative diseases is excitotoxicity which remain nebulous to date. Excitotoxicity is caused by over-stimulation of ionotropic glutamate receptors mainly NMDA receptors and lead to uncurbed accumulation of intracellular calcium ions. As a result there is substantial imbalances in the intracellular environment (regulation and signalling) that activate various programs of neuronal death. While many studies have done to find the whole proteome of mouse brain none have scrutinized the functional impairment of regulatory signalling proteins in excitotoxicity. We implemented for the first time a combination of phosphoproteomics and N-terminomics approach to understand two important post translation modifications (phosphorylation and truncation) of proteins during neuronal excitotoxicity in a time dependent manner. We quantified a total of 4755 phosphopeptides and 3843 N-termini. To unravel global phosphoproteome changes we deliberately choose a higher confident set of phosphopeptides (identified in two search engines) 34.1% of the total and ultimately found 156 and 397 phosphopeptides that significantly (±2 fold) fluctuate at two different time points in neuronal excitotoxicity. Besides changes in phosphoproteomes in excitotoxicity we found 98 and 509 cleavage sites in N-terminomics experiment. All the significantly dismayed proteins direct synaptic signalling defects (axonal guidance and signalling pathway (p < 0.01) during excitotoxicity. From these findings we can pinpoint the group of proteins that have dysregulated phosphorylation and truncation in excitotoxicity. Therefore, those proteins perturbed in excitotoxicity may suggest new directions in the investigation of the underlying molecular mechanisms accountable for the pathophysiological consequences of excitotoxicity.