Three-dimensional (3D) biodegradable polyglycolic acid fiber (PGA) preforms were developed as temporary scaffolds for three-dimensional tissue regeneration applications. Three-dimensional biodegradable polyglycolic acid fiber (PGA) preforms including various degrees of interlaced structures called 3D plain, semi-interlaced, and orthogonal woven preforms were designed. Analytical relations and finite element model-based software (TexGen) on fiber volume fraction and porosity fraction were proposed to predict scaffolds’ stiffness and strength properties considering micromechanics relations. It was revealed that yarn-to-yarn space, density, and angles of all 3D PGA fiber preforms were heterogeneous and demonstrated direction-dependent features (anisotropy). Total fiber volume fractions (Vfp) and porosity fraction (Vtpr) predicted by analytic and numerical modelling of all 3D scaffolds showed some deviations compared to the measured values. This was because yarn cross-sections in the scaffolds were changed from ideal circular yarn (fiber TOW) geometry to high-order ellipse (lenticular) due to inter-fiber pressure generated under a tensile-based macrostress environment during preform formation. Z-yarn modulus (Ez-yarn) and strength (σz-yarn) were probably critical values due to strong stiffness and strength in the through-the-thickness direction where hydrogel modulus and strengths were negligibly small. Morphology of the scaffold showed that PGA fiber sets in the preform were locally distorted, and they appeared as inconsistent and inhomogeneous continuous fiber forms. Additionally, various porosity shapes in the preform based on the virtual model featured complex shapes from nearly trapezoidal beams to partial or concave rectangular beams and ellipsoid rectangular cylinders. It was concluded that 3D polyglycolic acid fiber preforms could be a temporary supportive substrate for 3D tissue regeneration because cells in the scaffold’s thickness can grow via through-the-thickness fiber (z-yarn), including various possible mechanobiology mechanisms.