Abstract: With the fast advancement of the industry, including the drug and medical fields, Irregularity Descriptors may help to measure the physicochemical and Nano-properties, which are necessary for a growing industry. Biphenylene is a two-dimensional polymeric material that is among the most active areas of investigation in chemistry, biology, and physics. In our article, in view of structure analysis and mathematical derivation, we studied some topological descriptors such as the General Harmonic index, Redefined version of Zagreb indices, the Sombor index 𝑆𝑂, the General sum-connectivity index, First and Second multiplicative Zagreb index, Geometric arithmetic index, Ordinary Geometricarithmetic index Atom-bond connectivity (ABC) index and Irregularity Descriptors of molecular chain graphs of Biphenylene 𝐷𝑛. Furthermore, by the concepts of well-known degree-based descriptors, we introduced new degree-based descriptors such as (the Yemen-Sombor index) (𝑌𝑆 − 𝑖𝑛𝑑𝑒𝑥), Second General sum-connectivity index (𝜒2 𝛼 ), Third General sum-connectivity index (𝜒3 𝛼 ), Generalized General sum-connectivity index (𝜒𝛼 𝛼) of chain Biphenylene. These numerical values correlate with structural facts and chemical reactivity, biological activities, and physical properties. The results obtained could help us learn more about the characteristics of the chain Biphenylene.