[String.sub] Why would this NOT be subing???

You should definitely make this much simpler. Advanced is not the same thing as complicated. This script is complicated, not advanced.

Here's a list of things to make it better:

• foreach is deprecated. It's also a lot more confusing than just using pairs.
• CheckChat = function should be function CheckChat
• i is unused, name it _
• SubCount is a poor name. Maybe call it start or something meaningful
• if msg:sub(1, 2):find("/e") is the same thing as if msg:sub(1, 2) == "/e"
• You say Settings. 24 times. Make variables!
• Every single time Cmd and Cmd2 are used, you first add front to them. Just change the variable instead.

Here's some style things you should do:

• Pick one type of quote, don't use both ' and ". " is usually the preference (because of precedent from other languages)
• Put spaces around your operators and other symbols, especially .. and =. It makes it read so much easier, and you can even add extra spaces in places to indicate what things should be grouped
• Don't use the print "msg" style of calls, it's very inconsistent with the rest of Lua
• No point in wrapping things in parens, e.g, Cmd2. You don't need to when you have spaces (see above)
• Break long statements up. There's no point in having a line that does a ton of things if you can't understand it.
• or is associative, and (usually) commutative, so it doesn't make sense to put parentheses around these things.

Here is what I got:

function CheckChat(plr,msg)
    for _, v in pairs(_G.Commands) do
        local Cmd = v.Cmd:lower()
        local Cmd2 = v.Cmd2:lower()
        local start = 1
        if msg:sub(1, 2) == "/e" then 
            start = 3
        else 
            start = 1 
        end

        local mid, front = Settings.MiddlePrefix, Settings.FrontPrefix;
        Cmd = front .. Cmd
        Cmd2 = front .. Cmd2

        -- This doesn't make sense:
        local partOfMsg = msg:sub(start, #( (Cmd .. mid or Cmd ) or (Cmd2 .. mid or Cmd2) ))
        -- Neither does this:
        local commandCheck = (Cmd .. mid or Cmd) or (Cmd2 .. mid or Cmd2)

        if partOfMsg == commandCheck then
            print('got bypass msg:sub')
            if _G.GetRank(plr) <= v.Rank then
                print('got by getrank')

                -- This doesn't make sense:
                local before = (Cmd .. mid or Cmd) 
                    or (Cmd2 .. mid or Cmd2) 
                    or ((Cmd .. mid or Cmd) 
                    or (Cmd2 .. mid or Cmd2))

                msg = msg:sub(#before + 1)
                local r, e = ypcall(function()
                    v.Func(plr, msg)
                end)
                if not r then _G.Error(e) end
            else
                --You cant acess this command!
            end
        else
            --Sorry command was not found!
        end
    end
end

Now that we've done all this, there's a ton of stuff that makes no sense.

-- This:
#( (Cmd .. mid or Cmd )  or (Cmd2 .. mid or Cmd2) )
-- Is equivalent to this:
# ( Cmd .. mid )

so I have no idea what you were going after with the remainder of the script and all of the ors.

You cannot say if a == b or c. The precedence will make this if (a == b) or c, which is effectively just if true. Expressions cannot have "two values" at the same time. That's not what or does.