In this paper, we propose new algorithms for both ISE exploration and selection with considering important physical constraints such as pipestage timing and instruction set architecture (ISA) format, silicon area and register file. To handle these considerations, an ISE exploration algorithm is proposed. It not only explores ISE candidates but also their implementation option to minimize the execution time meanwhile using less silicon area. In ISE selection, many researches only take silicon area into account, but it is not comprehensive. In this paper, we formulate ISE selection as a multiconstrained 0-1 knapsack problem so that it can consider multiple constraints. Results with MiBench indicate that under same number of ISE, our approach achieves 69.43%, 1.26% and 33.8% (max., min. and avg., respectively) of further reduction in silicon area and also has maximally 1.6% performance improvement compared with the previous one.