Abstract Non‐centrosymmetric (NCS) structures are of great importance for the development of symmetry‐dependent functional properties, yet their rational structural design remains a great challenge. Herein, a strategy driven by a highly promising honeycomb structure framework that draws from nature has been proposed for designing three new NCS structures, La 4 O 4 (BO 3 ) 3 ·ClSr 3 and Sr 2 Y(BO 3 ) 4 ·XSr 3 (X = Cl, Br). They exhibit excellent nonlinear optical (NLO) properties, including strong second‐harmonic‐generation (SHG) responses (2.4–5.4 × KH 2 PO 4 (KDP)), short ultraviolet (UV) cut‐off edges ( λ cut‐off < 200 nm), and stable physicochemical properties, which make them promising UV NLO crystals. Furthermore, comparing their structures and properties with other compounds in the Gaudefroyite family, it has been found that they all have honeycomb‐like structures. With the continuous modification of their compositions, these structures can achieve not only structural transformation from centrosymmetric (CS) to NCS but also gradual doubling of SHG responses from Ba 4 (BO 3 ) 3 X 4 ·XBa 3 series (≈1 × KDP) to Sr 2 Y(BO 3 ) 4 ·XSr 3 series (≈2 × KDP) to La 4 O 4 (BO 3 ) 3 ·ClSr 3 series (≈6 × KDP). Moreover, the ON–OFF of their chiral structures can be achieved through modulating a honeycomb‐like framework and their infilling as observed in La 4 O 4 (BO 3 ) 3 ·BrBa 3 ( P 6 3 mc ), La 4 O 4 (BO 3 ) 3 ·ClSr 3 ( P 6 3 ) and Sr 2 Y(BO 3 ) 4 ·ClSr 3 ( P 6 3 mc ). These indicate that honeycomb is an ideal structural template for achieving the design of NCS structures.