After hours of working with this program, I’ve finally figured out how to successfully install and run old Nancy Drew games that are not Mac compatible (including 2-disk games) on a MacBook Pro (current iOS Sierra 10.12.1). I successfully played through several games using this process, so I know that it works! It’s possible that not every single one of these steps is required, but this is exactly how I did it, step-by-step, and it works.

There are a couple of games that don't run properly with this method, but I've only run into 2: Secrets Can Kill and Warnings at Waverly Academy (which runs, but plays very slowly).

You can download Wineskin Winery for free here: http://wineskin.urgesoftware.com/tiki-index.php?page=Downloads

1. Create a blank folder titled “[Title of game] Game Files”
2. Create a blank folder titled by the game acronym
3. Insert Disk 2 and explore through Finder
4. Copy all files from Disk 2 and paste them into your Game Files folder
5. Insert Disk 1 and explore through Finder
6. Copy all files from Disk 1 and paste them into your Game Files folder
7. Copy all files from Game Files folder into game acronym folder
8. When prompted, select “Keep Both” regarding duplicate files
9. Open Wineskin Winery
10. Make sure that Engine “WS8Wine.1.3.18″ is installed and selected
11. Click “Create New Blank Wrapper”
12. Title it by the game acronym
13. Install Wine Gecko Installer
14. Dismiss dialogue box
15. Close out installer (it shouldn’t have to successfully complete)
16. Dismiss dialogue box
17. Open wrapper through applications
18. Dismiss dialogue box
19. Open wrapper through applications again
20. Click “Install Software”
21. Click “Move a Folder Inside”
22. Find Game Acronym folder and select it
23. Select setup.exe file
24. Click “Advanced”
25. Click the box next to “Use Start.exe”
26. Click “Test Run”
27. When prompted to choose installation folder, delete everything from the path except for “C:\”
28. Proceed with installation
29. (If prompted for DirectX installation, deselect and do not install)
30. When prompted to view test run logs, select “Cancel”
31. Change executable file from “setup.exe” to “/Game.exe”
32. Click “Test Run”
33. You can now play this Nancy Drew game from your Applications!

Hope this is helpful for some of you!

EDIT: Danger By Design can be properly installed using engine WS8Wine.1.3.34. This should also work if you run into trouble with Creature of Kapu Cave and Last Train to Blue Moon Canyon. Thanks, /u/BlueMermaid333!

Also some games will not have their executable file listed as "Game.exe" but will have part of the title listed instead. For example, Warnings at Waverly Academy has "Waverly.exe" and Ransom of the Seven Ships has "Ransom.exe." Be sure to look for files like this if there is no "Game.exe!" Thanks, /u/ND_fan!