Cochlear implantation initiates an inflammatory cascade in which both acute insertion trauma and chronic foreign body reaction lead to intracochlear fibrosis and loss of residual hearing. Several strategies have been proposed to attenuate the local reactive process after implantation, including intracochlear drug delivery. The present study gives an overview of what is being investigated in the field of inner ear therapeutics and cochlear implant surgery. The aim is to evaluate its potential benefit in clinical practice. A systematic search was conducted in PubMed, Embase, and Cochrane Library databases identifying comparative prospective studies examining the effect of direct inner ear drug application on mechanical cochlear trauma. Both animal and human studies were considered and all studies were assessed for quality according to the validated risk of bias tools. Intracochlear administration of drugs is a feasible method to reduce the local inflammatory reaction following cochlear implantation. In animal studies, corticosteroid use had a significant effect on outcome measures including auditory brainstem response, impedance, and histological changes. This effect was, however, only durable with prolonged drug delivery. Significant differences in outcome were predominantly seen in studies where the cochlear damage was extensive. Six additional reports assessing non-steroidal agents were found. Overall, evidence of anti-inflammatory effects in humans is still scarce.