Promising drug agents are limited by their inability to reach in systematic circulation system when applied on skin, because of the excellent barrier of biological membranes, such as the stratum corneum (SC) of the skin. It is the outermost layer of the skin, SC, the principal barrier to all the topical application applied on skin. Various strategies were employed by many research group and pharmaceutical companies worldwide, for the formulation of microneedles. Therefore, microneedles (MN’s), used to puncture skin, it created the transient aqueous transport pathway and enhanced the trandermal permeability. Microneedles (MN’s) fabricated with natural and biodegradable polymer, such as carboxymethyl cellulose (CMC), and dextran. Inverse replication of micro milled master mould reproduced, solid out of natural polymeric microneedles, were subsequently assembled into transdermal patch and physiochemical characterized for dissolution index, mechanical strength constructed physical strong and uniform shape and size and inert profile. Although, dissolvable PVP and PVA based microneedle showed physical stability and MN’s, their different analyzed parameter is of promise for the fabrication matrix device of natural biodegradable polymeric microneedle transdermal drug delivery system.